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Editors:
Abdul Rohman
Susi Ari Kristina
Editors:
Published by:
Faculty of Pharmacy Universitas Gadjah Mada
Sekip Utara, Yogyakarta, 55281,
Indonesia
Pharmaceutical Scince & Clinical Pharmacy
Published by:
Faculty of Pharmacy Universitas Gadjah Mada
Sekip Utara, Yogyakarta, 55281,
Indonesia
ISSN : 2614-1779
No responsibility is assumed by the publisher for any injury and/ or damage to persons or
property as a matter of product liability, negligence or otherwise, or from any use or
operation of any methods, products, instructions or ideas contained in the material herein.
On behalf of the Editors, I am deeply grateful to all the reviewers who have been working
th
very hard for reviewing manuscripts submitted during the 5 International Conference on
Pharmacy and Advanced Pharmaceutical Sciences" held in Sheraton Hotel Yogyakarta,
by the Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia on
November 1 - 2, 2017
We would like to acknowledge to keynote speakers and all the distinguished speakers for
their valuable contribution during this conference. Further more, we also thank the steering
committee for their advice and support. Finally, I would appreciate to all participants, paper
and poster presenters who participated in the conference as w ell as cordially contributed
by submitting their full manuscripts published in this proceeding.
Finally, we believe that the presence of this proceeding will significantly contribute to
the advance scientific research, especially in the field of Pharmaceutical Science and
Thecnology.
Rina Kuswahyuning
th
The 5 International Conference on Pharmacy and Advance Pharmaceutical Science
The 5th International Conference on Pharmacy and Advance Pharmaceutical Science
Table of Content
Preface from Editor
Table of Content
The Comparison of Sodium Alginate and Xanthan Gum on Captopril 1–9
Release Profile of Floating Drug Delivery System Effervescent Capsule
Adeltrudis Adelsa D., Zakinza Karina AP, Ratna Triana SGZ, Dahlia
Permatasari
Red Betel Leaves (Piper crocatum RUIZ & PAV) Extract Granule Formula 27 – 38
and In Vivo Antiinflammatory Activity Studies
Laksmitawati DR, Kusumaningsih DA, Fahleni, Arifin MF 1
Utilization of Black Bali Rice (Oryza sativa L.) in Improving Insulin Activity 56 – 63
and Regeneration of Β-Cell Pancreas on White Diabetic Rat with Alloxan
Induced
Ketut Agus Adrianta, I Gusti Agung Ayu Kusuma Wardani
th
The 5 International Conference on Pharmacy and Advance Pharmaceutical Science
Health Related Quality of Life of Ischemic Stroke Patients in Yogyakarta 81 – 90
Measured With EQ-5D-5L
Muslimah, Tri Murti Andayani, Rizaldy Pinzon, Dwi Endarti
th
The 5 International Conference on Pharmacy and Advance Pharmaceutical Science
The Comparison Of Sodium Alginate And Xanthan Gum
Adeltrudis Adelsa D., Zakinza Karina AP, Ratna Triana SGZ, Dahlia
Permatasari
Pharmacy Study Program, Faculty of Medicine, Universitas Brawijaya, Jalan Veteran
65145 Malang, Indonesia
elsa.adam@ub.ac.id
ABSTRACT
Captopril is an antihypertensive therapy which also classified as BCS
(Biopharmaceutics Classification System) class III. It is mostly absorbed in the
stomach. The aim of this research was increasing the transit time of
captopril in stomach to improve permeability characteristics by comparing
two polymers, sodium alginate and xanthan gum. The chosen delivery
system is floating drug delivery system (FDDS) in capsule dosage.
Effervescent (sodium bicarbonate) was added to stimulate gas CO2 forming
and boost the floating. There are six formulas which made by wet
granulation method. The first three formula are using sodium alginate
percentage: F1 (5%), F2 (7,5%) and F3 (10%). The next three are designed in
captopril and xanthan gum ratio: F4 (50:21), F5 (50:42), and F6 (50:63). All
of the formulas have fullfiled the specification in flow characteristics, fines
percentages, homogeneity, organoleptic test, drug assay, weight diversity
and weight uniformity. The floating lag time takes less than 1 minute for all
of the formulas. We concluded F6 as the optimum formula. It has given the
long floating duration time and suitable with modified profile release
specification.
Keywords: captopril, sodium alginate, xanthan gum, release profile, floating,
capsule
INTRODUCTION
Captopril is one of antihypertensive choice classified as ACE
(Angiotensin Converting Enzyme) Inhibitor and often used as first line agent
on antihypertension therapy (Karakilic et al. 2012). Based on its
physicochemical characteristics, captopril is included in Class III BCS
(Biopharmaceutics Classification System). It has good solubility but low
permeability. The bioavailability of captopril is less than 90% (Shargel and Yu.
2005). In order to increase the permeability of captopril is increasing
retention time in gastric. The alternative modification is Gastro Retentive
Drug Delivery System (GRDDS) (Bhowmik et al. 2012). These kind of systems
increase drug retention time in gastric. It prolongs the contact between
gastric and drug to give the enough time for drug permeability.
There are several types of GRDDS, but floating drug delivery system
(FDDS) effervescent eas chosen (Arora et al. 2005). This system works by
produce gases from effervescent reaction and generate low density system
to be floated on gastric fluid. The carbon dioxide gases was obtained due to
reaction of sodium bicarbonate, as gas generating agent, and HCl in gastric
fluid (Khan and Bajpai. 2010). This system is applied in capsule dosage form.
Capsule is one of the famous solid dosage form which is easy to swallow
because of its smooth and slippery surface. The bulk was tamped into
granules using wet granulation method. One of the reason of granulation
choice is to modify the release of captopril.
Polymer is best used in modified release system. Sodium alginat and
xanthan gum are natural polymer. It has swelling ability and forms gel to
entrapped drugs. The advantages of natural polymer are non toxic,
biodegradable, biocompatible, cheap, easy to obtain and not accumulated in
specific organ (Sachan et al. 2009). The higher of sodium alginate
concentration has been used, the lower of cumulative percentage of drug
release would be yielded until 12 hours (Kumar et al. 2014).
Flowability
In this research, flowability was tested using the determination of flow
velocity and angle of repose. The instrument we used was Flodex™. As much
as 10 grams of captopril granules were weighed and counted how much time
do they need to flow. The result is stated in g/second (USP, 2006). After
flowing from the Flodex, the granules has formed cone. We measured the
height (h) and radius (r) to calculate angle of repose (α)
tan α = h/r............................................................(1)
Fines Percentage
As much as 5 grams of captopril granules were placed on sieve shaker
mesh number 80. The instrument was running for 5 minutes in amplitude 60.
We calculated the weight of granules passed the sieve using the equation
(Khan et al. 2010).
(prior weight-final weight)
% fines= x 100..........................(2)
prior weight
Organoleptic
The purpose of this test id identifying the physical appearance of FDDS
capsules (color, shape and odor).
Weight Uniformity
Randomly, 20 capsules were taken from each formula and weighed
respectively. The mean weight of 20 capsules were calculated. Deviation
percentage were calculated using this equation (Depkes RI, 1979):
(capsule weight – mean capsules weight)
% deviation = x 100
mean capsules weight
Weigh Diversity
As many as 10 capsules were weighed one by one. Then, capsules
were opened to pull out the granules. He empty capsules were weighed
thourougly The nett weight was calculated by substract capsule weight and
empty capsule weight. By the content uniformity (as stated in captopril
monography), we calculated captopril content on each capsule. The
assumption is that captopril is ditributed homogen (Depkes RI, 1995).
Drug Content
The granules were weighed as much as 300 mg (equal with 50 mg
captopril). The granules were mashed and dissolved in HCl 0,1N. The sample
was filtered and absorbance was measured using Spectrophotometer UV Vis
at maximum wavelength 201,8 nm. The absorbance was used to calculated
drug concentration using linear regression curve. The percentage of captorpil
are determined using this equation (USP, 2007):
(content measured)
% Drug Content = x 100 .....................................(3)
content on the label
Floating Duration
This test was observed as long as the release profile test was run. The
observation was made on these interval time : minutes 60th, 240th, 360th,
dan 480th. The total duration of this observation was 7-8 hours.
Release Profile
This test used similar Apparatus 2 floating duration. The amount of
captopril released were determined by sampling on these interval times: at
0,25th; 0,5th; 0,75th; 1th; 2th; 3th; 6th; and 8th hour. The amount of drug release
was measured using Spectrophotometer UV-Vis at maximum wavelength
(13)
Homogeneity
The datas shows that the drug content was suitable with the
spesification (not more than 98% and not less than 101,5%). The captopril
homogeneity was good because the RSD are less than 6% (BP, 2009).
Organoleptic
The capsules are ellipse, their color is white and blue. The surface of
capsule is clean, smooth and odorless.
Weight Uniformity
The capsules weight has uniformity. For capsules have mean weight
300mg or more, there were no 2 capsules which its deviation more than
7,5%
Weight Diversity
The weight diversity was suitable with the spesification. Their captopril
content not more than 98% and not less than 101,5%. The RSD are less than
6%.
Drug Content
Based on table 3, it can be concluded that all of the formulas
contained not more than 98% and not less than 101,5% captopril (Depkes RI,
1995).
Floating Duration
From Table 4, it can be concluded than the higher concentration of
polymer, the longer FDDS capsule could float on the gastric fluid.
Release Profile
According to Welling (1980), the release drug on the 2nd hours should
achieve 20-50%. At the 4th hours, the drug must 45-75%. Finally, at the 8th
hours, more than 80% drug has to be released. F3 and F6 have long floating
duration. They were also suitable with the specification of release profile.
But F6 has longer floating duration and at the 480th minutes, it has released
more than 80% of captopril (Table 5).
Release Kinetics
Based on calculation of R2 value from linear regression, the highest R2
at Higuchi plot for sodium alginate and xanthan gum F6 (Table 6). F4 and F5
xanthan gum are following Korsmeyer Peppas model. The Higuchi model
means that most of drug release is controlled by diffusion process.
CONCLUSION
It can be concluded F6 as the optimum formula. It has given the long
floating duration time and suitable with modified profile release
specification.
REFERENCES
American Pharmaceutical Association. 2007. USP 30-NF 25. The United States
Pharmacopeial Convention. USA.
Arora, S., Ali, J., Ahuja, A., Khar, R.K., dan Baboota, S. 2005. Floating Drug
Delivery Systems: A Review. AAPS PharmSciTech. 6(3): 372-390.
Bhowmik, D., Gopinath, H., Kumar, B.P., Duraivel, S., Sampath KP. 2012.
Controlled Release Drug Delivery Systems. The Pharma Innovation.
India.
British Pharmacopoeia. 2009. British Pharmacopoeia, Volume I & II.
Medicines and Healthcare Products Regulatory Agency (MHRA).
London.
Depkes RI. 1979. Farmakope Indonesia. Edisi III. Departemen Kesehatan RI.
Jakarta.
Depkes RI. 1995. Farmakope Indonesia. Edisi IV. Departemen Kesehatan RI.
Jakarta.
Karakilic, E., Buyukcam, F., Kocalar G., et al. 2012. Same Effect of Sublingual
and Oral captopril in hypertensive Crisis. Eur rev Med Pharmacoal Sci.
16:1642-1645
Khan, Azhar Danish, Meenakshi Bajpai. 2010. Floating drug delivery system:
An overview. International Journal of Pharmaceutical Technology
Research (2), 2497-2505.
Khan, AD, Bajpai, M. 2010. Floating Drug Delivery System: An Overview.
International Journal of PharmTech Research. 2(4): 2497-2505
Kumar, T.A., Velmurugan, S., Ravishankar, K., and Reddy, N. 2014.
Formulation and evaluation of flupirtine maleate sustain release
matrix tablets. Scholars Research Librar, Der Pharmacia Lettre. 6
(4):20-2
Sachan, N., Pushkar, S., Jha, A., Bhattcharya, A. 2009. Sodium alginate: the
wonder polymer for controlled drug delivery. Journal of Pharmacy
Research. India.
ABSTRACT
Amikacin is an effective aminoglycoside commonly used in the
treatment of gram negative bacterial infections. Serum drug concentration
monitoring is used to guide dosing while achieving target concentrations.
The aim of this report is to describe the importance of properly performed
drug concentration monitoring in a patient on amikacin treatment. A 66-
year-old woman with chronic renal failure was treated with amikacin for
Acinetobacter infection. Initiation of amikacin loading dose of 700 mg
resulted in peak drug concentration of about 24.25 mg/L. Subsequent dosing
was administered with random drug concentration monitoring. Pharmacists
in therapeutic drug monitoring service should utilize individual
pharmacokinetic parameters and suggest appropriate dosing regimen.
INTRODUCTION
Amikacin is one of the most common aminoglycoside that may use in
combination with β-lactams due to effective for the treatment of systemic
infections caused by most gram negative bacteria (Avert, et al., 2011).
However, aminoglycoside has toxic properties if it is used imprecisely.
The most common clinical toxicities of aminoglycosides found such as
nephrotoxicity, ototoxicity and others. The risk factors of toxicity include:
disease state, concurrent drugs used and prolonged therapy. Many strategies
to reduce the risk of toxicity of Aminoglycosides had been performed as
reported by Prayle, et al. (2010), such as to manipulate dosage regimens
individually and adherence to the application of pharmacokinetic rules.
Large amount research had reported about the dosage regimen
manipulation of amikacin use. Amikacin can be administered by multiple
doses or simpler single-dose. However, both must be monitored for serum
levels (Abd-Elfattah, et al., 2017).
CASE REPORT
A 66 year-old female (weight 70 kg) was treated at the Intensive Care
Unit of a General Hospital in Malaysia for suspected Acinetobacter infection.
Her current medical problems included diabetes mellitus, ischemic heart
disease, hypertension, dyslipidemia, and acute on chronic renal failure. Her
serum creatinine was 234 µmol/L (Creatinine clearance CrCL, was estimated
to be 22.3 mL/min).
Medications included digoxin, frusemide and ranitidine. Her antibiotics
were nystatin, metronidazole, ceftriaxone, and amikacin. Therapeutic drug
monitoring was requested for amikacin dosing. Following a 700 mg
intravenous loading dose, three more 500 mg intravenous doses were given
to this patient. Serum drug concentrations were measured randomly after
the doses were given.
The Figure below shows the concentration-time profile of amikacin.
DISCUSSION
The elimination of amikacin would be expected to be very slow in
patients with renal impairment. While the target peak concentration may be
independent of the renal function, the target trough concentration on the
other hand, depends on the drug clearance. Therefore, the ability to predict
when it is safe to give the subsequent dose is important. In the absence of
computer software to predict the pharmacokinetic parameters of the drug,
the best approach would be to obtain two concentrations within an
appropriate interval and use those values to estimate a suitable time to give
the next dose. Pharmacokinetic parameters calculated using two
concentration data can also be used to estimate the volume of distribution,
which could be used to estimate a suitable dose for the patient to achieve
the desired peak concentration.
A suitable time to give the next dose is when the trough concentration
of < 5 µg/L is achieved. In this patient, only one concentration was available
after the first loading dose was given. The second dose of 500 mg was
administered about 90 hours after the initial loading dose. However, it was
administered in the absence of suitable data that could be used to predict a
safe trough concentration.
Similarly, during the second and subsequent dosing intervals, only one
drug concentration value was available for each dosing interval. It is quite
difficult to predict how much dose is needed to achieve the target peak
concentration. The concentration-time profile shows that it was possible that
peak concentrations were not achieved during these dosing intervals. Renal
function in critically ill patients may change rapidly. As a result, drug
clearance which is dependent on renal function also changes rapidly.
Implementation of monitoring methods by the TDM service should give
meaningful and useful clinical information which can then be applied in the
management of drug dosing.
In this patient, monitoring of serum amikacin concentrations were
performed randomly and is unlikely to yield useful information. Although
several serum levels have been obtained from measurements from patients,
but planning in the routine procedure of amikacin administration is not
steady. In such patients, the need to quickly estimate a suitable
amikacin dosing regimen in order to achieve the desired therapeutic target is
very important.
CONCLUSION
The TDM was indicated in this patient but in the absence of suitable
pharmacokinetics computer software, the practice of random sampling
might not produce any suitable pharmacokinetic parameters, thus depriving
the patient of the benefits of TDM.
EKGNOWLEDGEMENT
I am grateful to all those who support this work as well to the Head of
Clinical Department, School of Pharmaceutical Sciences, Universiti Sains
Malaysia, Pulau Pinang Malaysia for facilities provided during the recording
of this case.
REFERENCES
Ab Rahman, A. F., Ahmed Abdelrahim, H. E., & Mohamed Ibrahim, M. I.
(2013). A survey of therapeutic drug monitoring services in Malaysia.
Saudi Pharm J, 21(1), 19-24. doi: 10.1016/j.jsps.2012.01.002
Abd-Elfattah, R., Elhdad, A.M. A., Khames, A., Abdelrahim, M.E.A., &
Shouman, S.A. (2017). Efficacy and toxicity of once versus twice daily
regimens of amikacin in febrile neutropenic pediatric cancer patients.
Beni-Suef University Journal of Basic and Applied Sciences,6(1),76-
82.doi: https: //doi.org/10.1016/j.bjbas. 2017. 01.006
Avent, M.L., Rogers, B.A., Cheng, A.C., & Paterson, D.L. (2011). Current use of
aminoglycosides: indications, pharmaco-kinetics and monitoring for
toxicity. Intern Med J, 41(6), 9. doi: 10.1111/j.1445-5994.2011.
02452.x.
Blackburn, L.M., Tverdek, F.P., Hernandez, M., &Bruno,J.J.(2015).First-dose
pharmaco-kinetics of aminoglycosides in critically ill haematological
malignancy patients. Int J Antimicrob Agents, 45(1), 46-53. doi:
10.1016/j.ijantimicag.2014.09.006
Botev, R., Mallie, J.P., Wetzels, J. F., Couchoud, C., & Schuck, O. (2011). The
clinician and estimation of glomerular filtration rate by creatinine-
based formulas: current limitations and quo vadis. Clin J Am Soc
Nephrol, 6(4), 937-950. doi: 10.2215/CJN.09241010
Dijkstra, J.A., van Altena, R., Akkerman, O.W., de Lange, W.C.M., Proost, J.H.,
van der Werf,T.S.,Alffenaar,J.W.C.(2015).Limited sampling strategies
for therapeutic drug monitoring of amikacin and kanamycin in patients
with multi drug-resistant tuberculosis. International Journal of
Antimicrobial Agents, 46(3), 332-337.
Oliveira, J.F.P., Cipullo, J.P., & Burdmann, E. A. (2006). Aminoglycoside
Nephroto-xicity. Braz J Cardiovasc Surg, 21(4), 8.
Raveh, D., Kopyt, M., Hite, Y., Sonnenblick, M., & Yinnon, A.M. (2002). Risk
Factors For Nephrotoxicty in Elderly Patients Receiving Once-Daily
Aminoglycosides Q J Med, 95, 7.
Roger, C., Nucci, B., Molinari, N., Bastide, S., Saissi, G., Pradel, G., . . . Muller,
L. (2015). Standard dosing of amikacin and gentamicin in critically ill
patients results in variable and subtherapeutic concentrations.
[Observational Study Research Support, Non-U.S. Gov't]. Int J
Salgado, J.V., Neves, F.A., Bastos, M.G., França, A.K., Brito, D.J., Santos, E.M.,
& Salgado Filho, N. (2010). Monitoring renal function: measured and
estimated glomerular filtration rates, a review. Brazilian Journal of
Medical and Biological Research, 43(6), 528-536. doi: 10.1590/ s0100-
879x2010007500040
Sandu, J.S., Sebgal, A., & Singh, A. (2007). Aminoglycoside Nephrotoxicity
Revisit-ed.JIACM, 8(4), 3.
White, B.P., Lomaestro, B., & Pai, M. P. (2015). Optimizing the initial amikacin
dosage in adults. [Clinical Trial]. Antimicrob Agents Chemother, 59(11),
7094-7096. doi: 10.1128/AAC.01032-15
ABSTRACT
The aim of this study was to observe the use of analgesic pattern and
pain intensity outcomes in postoperative patients. The study was conducted
on postoperative patients at Universitas Airlangga Teaching Hospital
Surabaya in the periode of April to Mei 2017. Recording the use of analgesics
and pain assessment was done during hospitalization, at early postsurgical
until the patients discharge. Results of 116 patients’ postoperative patients
showed the analgesics used were mefenamic acid, ketorolac, metamizole,
paracetamol and tramadol used as a single and analgesics combination.
Combination therapy was got by 45% of patients. Pain assesment showed
75% of patients without pain and mild pain, 24% with moderate pain, 2% got
severe pain at the early postsurgical. At discharge time 97% of patients
without pain and mild pain, 3% with moderate pain, and no patient with
severe pain. Inconclusion, nociceptic pain experienced by postoperative
patients and pain management has provided good outcomes, but there are
still 2% of patients with severe early postoperative pain requiring better
management from interprofessional health care.
not been optimal (Apfelbaum and Chen, 2003). Globally, the prevalence of
postoperative pain ranges from 50% to 75% of total surgical patients (Philip
et al., 2007). More than 80% of patients undergoing surgical procedures
experience acute postoperative pain and about 75% of those reported
postoperative pain with severity ranging from moderate, severe or extreme
(Gan et al., 2014). Other studies have reported that 41% of patients
experience postoperative pain with moderate and severe pain levels on day
0. Even, the prevalence of moderate and severe pain was increased in the
type of abdominal surgery, extremity surgery, and back/spinal surgery
(Sommer et al., 2008).
Unresolved acute pain can provide significant psychological
consequences, starting from uncomfortable sleep to the stage of
development of Post-Traumatic Stress Disorder (PTSD) (Tennant, 2004).
Handling of inadequate pain therapy can have a negative effect on quality of
life, recovery of body function, risk of complications and postoperative
painful pain. In addition, the patient's rehabilitation process can be delayed,
resulting in longer hospitalization time (Morrison et al., 2003). Other effects
that may arise include increased risk of side-effects, such as the development
of chronic disease, suppression of immune cells, long wound healing
operations, and increased activation of adrenergic hormones and their risks
in the form of coronary heart disease or gastrointestinal cell damage,
difficulty in moving can trigger thromboembolism (Misiołek et al., 2014).
Analgesics are necessary for adequate postoperative pain control to avoid
postoperative complications and speed up the recovery process of patients
(Chaturvedi and Chaturvedi, 2007; Clark, 2002). To overcome pain
effectively, several factors need to be considered, from the cause of pain,
degree of pain, type selection and analgesic dosage to be used, route of
administration, and frequency of administration (Apfelbaum and Chen,
2003). The aim of this study is to observe the use of analgesic patterns and
pain intensity outcomes in postoperative patients.
Number of patients
Analgesic Regimentation
1 day 2 days 3 days 4 days 5 days 10 days
3x10mg iv 1
Ketorolac
3x30mg iv 60 12 2 1 1
3x30mg iv 1
3x50mg iv 1
3x100mg
Tramadol 26 6 1 1
intermittent iv
2x50mg iv 1
2x1tab oral 1
1x1g iv 7
2x1g iv 4
Metamizole
3x1g iv 9 10 1 1 1
3x1 tab oral 1
3x500mg oral 3 2 1
4x500mg oral 3 1 2
4x1000mg oral 1
Paracetamol 4x750mg
1
intermittent iv
3x1000mg
3 2
intermittent iv
Mefenamic 3x500mg PO 32 12 1
Fentanyl
1x12,5mg 1
patch
Figure 2. Initial and before discharge Postopera Pain intensity in surgery units
CONCLUSION
In conclusion, postoperative pain management in Universitas Airlangga
Hospital has provided good outcomes, but there are still 2% of patients with
severe early postoperative pain requiring better management from
interprofessional health care.
ACKNOWLEDGEMENT
We are grateful to Universitas Airlangga Teaching Hospital for
permission doing this research.
REFERENCES
American Society of Anesthesiologists Task Force on Acute Pain
Management, 2012. Practice guidelines for acute pain management in
the perioperative setting: an updated report by the American Society of
Anesthesiologists Task Force on Acute Pain Management.
Anesthesiology 116, 248–73.
Apfel, C.C., Turan, A., Souza, K., Pergolizzi, J., Hornuss, C., 2013. Intravenous
acetaminophen reduces postoperative nausea and vomiting: A
systematic review and meta-analysis. Pain 154, 677–689.
Apfelbaum, J.L., Chen, C., 2003. Postoperative pain experience: results from
a national survey suggest postoperative pain continues to be
undermanaged. Anesth. Analg. 97, 534–40.
Chaturvedi, S., Chaturvedi, A., 2007. Postoperative pain and its management.
Indian J. Crit. Care Med. 11, 204.
Chou, R., Gordon, D.B., De Leon-Casasola, O. a., Rosenberg, J.M., Bickler, S.,
Brennan, T., Carter, T., Cassidy, C.L., Chittenden, E.H., Degenhardt, E.,
Griffith, S., Manworren, R., McCarberg, B., Montgomery, R., Murphy, J.,
Perkal, M.F., Suresh, S., Sluka, K., Strassels, S., Thirlby, R., Viscusi, E.,
Walco, G. a., Warner, L., Weisman, S.J., Wu, C.L., 2016. Management of
postoperative pain: A clinical practice guideline from the American pain
society, the American society of regional anesthesia and pain medicine,
and the American society of anesthesiologists’ committee on regional
anesthesia, executive commi. J. Pain 17, 131–157.
Clark, J.D., 2002. Chronic pain prevalence and analgesic prescribing in a
general medical population. J. Pain Symptom Manage. 23, 131–137.
doi:10.1016/S0885-3924(01)00396-7
Duttchen, K.M., Lo, A., Walker, A., McLuckie, D., De Guzman, C., Roman-
Smith, H., Davis, M., 2017. Intraoperative ketorolac dose of 15 mg
versus the standard 30 mg on early postoperative pain after spine
surgery: A randomized, blinded, non-inferiority trial. J. Clin. Anesth. 41,
11–15.
Gan, T.J., Habib, A.S., Miller, T.E., White, W., Apfelbaum, J.L., 2014.
Incidence, patient satisfaction, and perceptions of post-surgical pain:
results from a US national survey. Curr. Med. Res. Opin. 30.
Gopalraju, P., Lalitha, R.M., Prasad, K., Ranganath, K., 2014. Comparative
study of intravenous Tramadol versus Ketorolac for preventing
postoperative pain after third molar surgery - A prospective
randomized study. J. Cranio-Maxillofacial Surg. 42, 629–633.
Hawker, G. a., Mian, S., Kendzerska, T., French, M., 2011. Measures of adult
pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for
Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill
Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short
Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and
Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res. 63, 240–
Jawaid, M., Muhammad, S., Shafiq, F., Malik, K.A., 2009. Acute postoperative
pain management by a surgical team in a tertiary care hospital: Patients
satisfaction. Middle East J. Anesthesiol. 20, 405–410.
Jensen, M.P., Chen, C., Brugger, A.M., 2003. Interpretation of visual analog
scale ratings and change scores: A reanalysis of two clinical trials of
postoperative pain. J. Pain 4, 407–414.
Khalili, G., Janghorbani, M., Saryazdi, H., Emaminejad, A., 2013. Effect of
preemptive and preventive acetaminophen on postoperative pain
score: A randomized, double-blind trial of patients undergoing lower
extremity surgery. J. Clin. Anesth. 25, 188–192.
McEvoy, G.K., 2011. AHFS Drug Information Essential. American Society of
Health-System Pharmacists, Maryland.
Memis, D., Inal, M.T., Kavalci, G., Sezer, A., Necdet, S., 2010. Intravenous
paracetamol reduced the use of opioids, extubation time, and opioid-
related adverse effects after major surgery in intensive care unit. J. Crit.
Care 25, 458–462.
Misiołek, H., Cettler, M., Woroo, J., Wordliczek, J., Dobrogowski, J., Mayzner-
Zawadzka, E., 2014. The 2014 guidelines for post-operative pain
management. Anaesthesiol. Intensive Ther. 46, 221–244.
Morrison, R.S., Magaziner, J., McLaughlin, M.A., Orosz, G., Silberzweig, S.B.,
Koval, K.J., Siu, A.L., 2003. The impact of post-operative pain on
outcomes following hip fracture. Pain 103, 303–11.
Motov, S., Yasavolian, M., Likourezos, A., Pushkar, I., Hossain, R., Drapkin, J.,
Cohen, V., Filk, N., Smith, A., Huang, F., Rockoff, B., Homel, P., Fromm,
C., 2017. Comparison of Intravenous Ketorolac at Three Single-Dose
Regimens for Treating Acute Pain in the Emergency Department: A
Randomized Controlled Trial. Ann. Emerg. Med. 70, 177–184.
Nikolova, I., Petkova, V., Tencheva, J., Benbasat, N., Voinikov, J., Danchev, N.,
2013. Metamizole: A review profile of a well-known “forgotten” drug.
part ii: Clinical profile. Biotechnol. Biotechnol. Equip. 27, 3605–3619.
Pasero, C., Stannard, D., 2012. The Role of Intravenous Acetaminophen in
Acute Pain Management: A Case-Illustrated Review. Pain Manag. Nurs.
13, 107–124.
Philip, W., Kuo, P.C., Schroeder, R.A., 2007. The postoperative care of the
surgical patient, in: David, D.O. (Ed.), First Exposure to General Surgery.
McGraw - Hill Co, pp. 93–97.
Pogatzki-zahn, E.M., Segelcke, D., Schug, S. a, 2017. Postoperative pain —
from mechanisms to treatment. PAIN Reports 2, e588.
Shargel, L., Yu, A., Wu-Pong, S., 2012. Applied Biopharmaceutics &
Pharmacokinetics, Sixth Edition, 6th ed. McGraw-Hill Education /
Medical, New York.
Sim, R., Cheong, D.M., Wong, K.S., Lee, B.M.K., Liew, Q.Y., 2007. Prospective
randomized, double-blind, placebo- controlled study of pre- and
postoperative administration of a COX-2- specific inhibitor as opioid-
sparing analgesia in major colorectal surgery. Color. Dis. 9, 52–60.
Sommer, M., Rijke, J.M. de, Kleef, M. van, Kessels, A.G.H., Peters, M.L.,
Geurts, J.W.J.M., Gramke, H.-F., Marcus, M.A.E., 2008. The prevalence
of postoperative pain in a sample of 1490 surgical inpatients. Eur. J.
Anaesthesilogy 25, 267–274.
Spacek, A., Goraj, E., Neiger, F.X., Jarosz, J., Kress, H.G., 2003. Superior
postoperative analgesic efficacy of a continuous infusion of tramadol
and dipyrone (metamizol) versus tramadol alone. Acute Pain 5, 3–9.
Strom, B.L., Berlin, J.A., Kinman, J.L., Spitz, P.W., Hennessy, S., Feldman, H.,
Kimmel, S., Carson, J.L., 1996. Parenteral Ketorolac and Risk of
Gastrointestinal and Operative Site Bleeding: A Postmarketing
Surveillance Study. J. Am. Med. Assoc. 275, 376–382.
Tennant, F., 2004. Complications of Uncontrolled, Persistent Pain. Pract. Pain
Manag. 4, 11–14.
Wu, C.L., Raja, S.N., 2011. Treatment of acute postoperative pain. Lancet
377, 2215–2225.
ABSTRACT
Red betel leaves (Piper crocatum Ruiz & Pav) contains flavonoid,
saponin, and tannin which have antiinflammatory activity against paw
edema with albumin as inducer. This research aims to determine the
optimum granule formula from red betel leaves dry extract which physically
and chemically stable and also effective as an antiinflammatory agent. This
study used 22 factorial design with 2 factors, red betel leaves extract and PVP
concentration as a binder. The evaluation result of physical appearance and
chemical properties were analyzed using Minitab 16 program then made
contour plots and contour plot superimposed. The optimum formula was
obtained from the contour plot superimposed on the levels of extract dose
2.55 gram and 1% PVP concentration. Furthermore, the optimum formula
was tested for antiinflammatory activity and showed edema inhibition
percentage of 44,65% against the negative group and no significance
difference with positive group, Na diclofenac 9mg/kgBB.
Keywords: Red betel leaves, antiinflammation, granule
INTRODUCTION
Inflammation is the local physiological response against tissue injury.
Arthritis gout is one example of disease that is accompanied by
inflammation. Arthritis gout is an inflammatory process caused by acid
crystalline desposition around the joints. Medication conducted for gout’s
patients were decreasing the production of uric acid serum with the xanthine
oxidase enzyme inhibitors as well as supressing the inflammatory response
with the antiinflammatory drugs. There are two classes of antiinflammatory
drugs i.e corticosteroids and Non Steroidal Antiinflammatory drugs
(NSAID’s). The use of these drugs are known cause adverse drug reaction,
such as gastric disorders. Therefore, treatment with herbal medicine could
be an alternative with fewer side effects1.
Formula (%)
No Materials
F1 F2 F3 F4
1 Red betel dried extract granule 2,28 g 2,85 g 2,28 g 2,85 g
2 PVP 0,5 0,5 2 2
3 Erythrosine 0,05 0,05 0,05 0,05
4 Aspartame 2 2 2 2
5 Na benzoate 0,1 0,1 0,1 0,1
6 Aerosil 0,5 0,5 0,5 0,5
7 Lactose ad 100 ad 100 ad 100 ad 100
2. Moisture Content
5 grams of wet granule were placed into petri disc and dried in the
oven temperature 40-60°C for 15 minutes. Granule was dried until constant
weight.
3. Flow Properties
a. Flow rate
The flow rate was determined by allowing 25 grams granules flow
through a funnel and fall freely onto a graph paper. The time of granule to
flow was measured using stopwatch.
b. Angle of Repose
The angle of repose was determined by allowing granules to flow
through a funnel and fall freely onto a graph paper on a horizontal surface.
The height and diameter of the resulting cone were measured and the angle
of repose is calculated from this equation:
Tan α =
α : angle of repose
h : granule height
r : radius of granule cone
5. Dissolve Time
In vitro dissolve time was measured by pouring a tea bag granule in a
beaker containing 200 mL of water (temperature 40°±2,5°C) and stirred for
20 times. Dissolve time was measured using stopwatch.
6. pH
pH were tested using pH meter.
[ ) ( )
Edema inhibition percentage = ( ( )
x
100%
Granule Formulation
Granule formulation were done using wet granulation methods. The
selection of this method is based on the properties of dried extract, which
had small density and voluminous properties, so the granulation were done
to increase the density. Granulation were also done to fix the the flow
properties of extract and reduce the dust formation. In a granulation, binder
played an important role as a material which had cohesive properties so that
capable to aglomerate dry powder particles forming a strong granule bond
after drying process 5.
bigger concentration of PVP, which the concentration were 2%. The bigger
concentration of PVP will make the stronger bond between granule particles
so it needed the longer time for granule to dissolve.
Granule dissolve time were important to test because instant granule
expected to be perfectly dissolve in a short time, so it can be used
immediately and provide optimal effects. Further results from the evaluation
of pH granule showed that the four formula had an acidic pH. It was
complied to the literature that red betel leaves had an acidic pH because of
the flavonoid antocyanin in the extract which also an acidic.
Based on the result of particle size distribution evaluation on table IV,
it was showed that the range of average diameter particle size granule
formula I-IV between 369,01 µm – 425,34 µm. According to the literature,
granule with particle size ≥250 µm had free flowing properties 7 . It can
concluded that all of the formula had a good flow properties so it will freely
flow in the packing machine and ensure the accuracy of doses. A fine granule
also has a narrow particle size distribution and the amount of fines was not
more than 10%. The evaluation result showed that all of the formula has a
narrow particle size distribution and followed the normal curve as can be
seen in Fig. 1. Thus it can be concluded that the particle size distribution of
granules were distributed properly.
Fig 2. Contour plot moisture content Fig 3. Contour plot flow rate vs PVP
vs PVP and extract concentration and extract concentration
Fig 4. Contour plot angle of repose vs Fig 5. Contour plot dissolve time vs
PVP and extract concentration PVP and extract concentration
Fig 6. Contour plot pH vs PVP and Fig 7. Contour plot super imposed
extract concentration
From the contour plots, it showed that the increasing of extract dose
will also increase the moisture content and granul dissolve time. It was
affected by the hygroscopic properties of dried extract. The increased of
extract dose will also lowering pH because of the flavonoid compounds
which classified as an acid. Beside the dose, increasing PVP concentration
will also increase moisture content, flow rate, and angle of repose. PVP will
form a strong bond between granule particles so it can enhance the cohesive
between particle and made a spheric granule. The spheric granule will
reduce particle friction so it will made a good flow rate. From each contour
plot then made the overlay contour plot or contour plot superimposed to get
the optimum formula. The white area in figure 1 determined the optimum
composition of formula. We choose red betel leaves dry extract at
concentration 2,55 grams and 1% of PVP as the optimum formula to be
tested its anti-inflammatory activity. Contour plot super imposed can be
seen in Figure 7.
CONCLUSION
The optimum granule formula of red betel leaves dried extract were
obtained at the level of extract dose 2,55 grams and PVP concentration 1%.
These formula had an in vivo antiinflammatory activity against albumin-
induced rat paw edema with inhibition percentage of 44,65% at dose 315
mg/kg BW compared with control group and no significant difference with
the positive control sodium diclofenac (dose of 9mg/kgBW) which had
edema inhibition percentage of 50,02%.
REFERENCES
1.Pradhan, D., Suri, K. a, Pradhan, D. K. & Biswasroy, P. Golden Heart of the
Nature : Piper betel L .J. Pharmacogn. Phytochem. 2013,1, 147–167
2.Hainer BL, Matheson E, Wilkes T. Diagnosis, Treatment, and Prevention of
Gout. American Family Physician. 2014; Volume 90, No 12. p 831-836
3.Steven, Laksmitawati DR., Helisa N. Antigout Prospects of Ethanolic Extract
from Red Betel Leaf (Piper crocatum Ruiz & Pav) Through Anti-
hyperuricemic and Anti-Inflammatory Evaluations on Sprague Dawley
Rats. Proceeding Book The 2nd International Conference on
Pharmaceutical Nanotechnology/Nanomedicine 2015. Faculty of
Pharmacy University of Pancasila. 2015.p 91-98
4.Food and Drug Supervisory Agency of the Republic of Indonesia. Regulation
of the Head of the Food and Drug Supervisory Agency of the Republic
of Indonesia No. 12 concerning the quality requirements of Traditional
Medicine. Jakarta: Directorate General of Drug and Food Control;
2014. h. 12
5.Lachman L, Lieberman HA, Kanig JL. Teori dan Praktek Farmasi industri Ed
III Vol. 1. diterjemahkan oleh Siti Suyatmi. Jakarta: UI Press; 2007.
h.227-257
6.Voigt. Buku pelajaran teknologi farmasi. Diterjemahkan oleh Soendani N.
S., Yogyakarta: UGM Press; 1995, h. 171-73; 201-03
7. Aulton ME. Pharmaceutics, The Science of Dosage Forms Designs. London:
Churchill Livingstone; 2007,
8. Senewe M, Yamlean P, Wiyono W. Uji efek antiinflamasi ekstrak etanol
daging buah labu kuning (Cucurbita moschata D.) terhap edema pada
telapak kaki tikus putih jantan galur wistar (Rattus novergicus).
Pharmacon Jurnal Ilmiah Farmasi. 2013; 2(01): h.75-80
9. Ana GL et al. Flavonoids as Anti-inflammatory Agents: Implications in
cancer and cardiovascular disease. Inflamm. Res. 2009; 58: p.537–55
ABSTRACT
The root of Dadangkak (Hydrolea spinosa L) is a herbal plant that
commonly used by South Kalimantan people for antidiabetic. The main
purpose of this research are : to examine the activity of ethyl acetate fraction
from EtOH fraction of the roots of dadangkak and to identify the chemical
contents of the roots by using Thin Layer Chromatography (TLC). The extract
of ethanol from 10 grams of the roots is yielded from materation then
fractionation by ethyl acetate. Wistar male rats is divided into three groups
(five rats each groups ). The first group is given glibenclamide 0.45 mg/kgBW;
the second group is given aquades 2 ml/200 gBW; and the last group is given
100 mg/kgBW ethyl acetate fraction perorally. Each group deliberately made
suffered from diabetes by giving induction of 150 mg/kgBW Aloxan
intraperitoneally. The measurement of blood glucose was held at the 1st, 4th,
and 12th by using Gluco-DR. the assay treatment had been done for 7 days
(from the 5th until 11th day). The result then being analysed with SPSS by
confidence level 95%. The ethyl acetate fraction of the plants was being
identified by using reagent solutions and TLC. The result showed the decline
of blood glucose level after the suspention was given significantly (sig<0.05)
compared to the control group with blood glucose level 162 ± 8,631 mg/dL
(at the 12th day). The chemical content of the ethyl acetate fraction showed
positive result to the saponin triterpenoid with Lieberman Burchard (LB)
reagent by showing the brown ring. Then, TLC assay was done by using n-hex
: ethyl acetate (2 : 6) and showed 2 violet spots after being sprayed by LB
reagent (with Rf point : 0.5 and 0.69 ). From the TLC assay can be guessed
that the sample contained saponin triterpenoid.
INTRODUCTION
Diabetes mellitus (DM) is a metabolic symptoms that appear on
someone caused by the increase of blood glucose consequence from the
damage or resistance of insulin (Scarano et al., 2006). The number of people
who suffer diabetes is increasing year by year. In 2000, the number of people
who suffer diabetes in Indonesia is 8,4 million people and estimated will
reach 21,3 million people in 2030. That case leads Indonesia to be the fourth
country with the highest number of diabetic sufferer after India, China, and
United States of America (Wild et al, 2004; For, 2008).
The high prevalence of diabetes mellitus makes people concern about
how to cure this disease. Concept of “back to nature-treatment” lately
become so famous and can be alternative of this treatment. Dadangkak
((Hydrolea spinosa L) is one of herbal plants that been used to cure DM in
South Kalimantan. the roots of Dadangkak is boiled with water and then the
water is drunk daily to decrease the blood glucose.
Experiment of using Dadangkak as antidiabetes before was only
observation datas (Widuri et al., 2004). The similar experiment was
conducted to evaluate the activity of ethyl acetate fraction of Chaenomeles
sinensis (Thouin) showed the ability to reduce cell damage caused by STZ
induction significantly (Sanchetti et al., 2017). Besides, the experiment of
Zanata et al. (2007) used the ethyl acetate fraction of Vitex megapotamica
(400 dan 800 mg / kg) leaves showed maximum hipoglicemic effect (each
28% and 20%) on mice that induced by Aloxan.
This experiment was conducted by examining the activity of roots of
Dadangkak as antidiabetes. The examination was counducted by giving the
ethyl acetate fraction from ethanol extract to Wistar diabetic male rats.
Induction of diabetes used 150 mg/kg of weights (i.p). Phytochemical
examination was conducted to identify the component of ethyl acetate
fraction. The main purposes of this experiment are to examine the activity
antidiabetes from ethyl acetate fraction of roots of Dadangkak and to
identify the chemical compenents of the ethyl acetate fraction that potential
as antidiabetes based on the Thin Layer Chromatoghraphy profiles.
Instruments
The instruments that have been used are beaker glass, test tubes,
shelf test tube, Bunsen, tripod, analytical balance, Gluco-DR, strips of Gluco-
DR, materation vessel, vortex, waterbath, separation funnel, spuit, vacuum
rotary evaporator, volumetric pipette, drop pipette, and cage
Procedures
Simplisia Treatment
Dadangkak obtained from Marabahan, South Kalimantan. The
sampling is first conducted from whole part of the plant, then parted the
roots. the roots is brown with soft texture then washed by water. This was
held to wash-out the impurities on the roots.
Sample then cut and dried by wind automatically. This was held to
decrease the water content so that damage risk caused by microorganism
can be stopped. Dried sample was blended to be powder so that the
extraction process would be easier. The simplisia powder then saved in the
vacuum container.
Antidiabetes Activity
The examination of antidiabetes activity used Wistar male rats age 2-3
months with 200-250 grams weight. The rats was divided into 3 groups (each
5 rats) : 1. Glibenclamide 0,4525 mg/kgBW, 2. Aquades 2ml/200 gramBW, 3.
Ethyl acetats of roots of Dadangkak perorally.
Dosage fraction that been used based on the result of dosage
orientation. Before that, all of the male rats were fasting for 16 hours. All
groups wer given Aloxan 150 mg/kgBW at the first day to increase the blood
glucose. The examination of blood glucose was conducted by Gluco-DR. the
examination then was conducted again at the fourth day to check if the
blood glucose increased. If the blood glucose increased, then the giving of
sample held at 5th day until 11th . the examination then held again at the 12th
day. The blood glucose that have been obtained then analyzed with SPSS
(confidence level : 95%).
Antidiabetes Activity
This experiment was a Diabetes Type I that related with pancreas
damage caused by diabetogenic compounds. Aloxan can destroy β
Mean value of rats’ blood glucose at the first day shows normal
condition. At the fourth day shows that the blood glucose level reached the
DM range either on the test group or control group. The effect of giving the
sample and control at the 5th day until 11th day was evaluated from the
blood glucose level at the 12th day. On that day the blood glucose level
showed stabil increment at the negative control and decrement at the
positive and fraction groups.
The result of mean value of blood glucose level at the 12th day could
be seen at the diagram below.
The mean value of blood glucose level at the 12th day showed
significant differences, which negative control was still on DM range, in other
hand positive control and ethyl acetate fraction have an ability to decrease
blood glucose level.
Data analysis used SPSS program with confidence level 95%. The result
of normality test Kolmorgov-Smirnov showed that the datas are distributed
normally (sig>0,05) and the homogenity test Levene datas which were being
tested were homogeny (sig>0,05) so that the test are continued with One
Way ANOVA. The result of One Way ANOVA showed that there were
significant differences between control and treatment groups (sig<0,05). To
examine the differences this analysis were continued with Turkey HSD test as
shown table 2 below,
From the result above, known that blood glucose level at Male rats
control groups showed the lowest blood glucose level 140 ± 13,76 mg/dL.
Mean value of blood glucose level can be set as standart to examine the
increment and decline because the effect of treatment. Positive control and
ethyl acetate fraction showed the significant difference compared to
negative control (sig<0,05). This means that positive control and ethyl
acetate fraction could decrease the blood glucose level of Male rats. Ethyl
acetate fraction can decrease the blood glucose level until 162,0 ± 8,63
mg/dL although cannot defeat the effect of positive control (sig<0,05).
Note : (a) : UV 254 nm ; (b) : UV 366 nm ; (c) : LB ; (d) : illustration; Rf : 0,5 & 0,69 : (+) saponin
CONCLUSION
Ethyl acetate fraction could decrease the blood glucose levels
significantly (sig<0.05) compared to control groups and have potential to be
observed further as antidiabetes.ethyl acetate fraction gave positive result to
saponin triterpenoid with LB reagent by showing the brownish ring on the
solution. TLC profile with n-hexane : ethyl acetate (2:6) as eluent was
obtained two spots colored violet after sprayed with LB reagent. Rf value
was 0,5 and 0,69 and said that the sample were expected contain saponin
type triterpenoid.
ACKNOWLEDGEMENT
We gratefully acknowledge that we would like to say thank to
Kementerian Riset Teknologi and Pendidikan Tinggi for the grant
experimental funding so that this experiment could be done fluenty and on
time.
REFERENCES
For W.C. 2008. The role of nutrition in diabetes management: From basic to
recent advances. Paper presented at the meeting of Persada
Conference Plenary Lecture Session. Malang.
Fiana N and Oktaria D. 2016. Pengaruh Kandungan Saponin dalam Daging
Buah Mahkota Dewa (Phaleria macrocarpa) terhadap Penurunan
Kadar Glukosa Darah. Jurnal Majority, 5(4): 128-132.
Lavle N, Shukla P and Panchal A. 2016. Role of flavonoids and saponins in the
treatment of diabetes mellitus. J Pharm Sci Bioscientific Res. 6(4): 535-
541
Nugroho A.E. 2006. Animal models of diabetes mellitus: Pathology and
mechanism of some diabetogenics. Biodiversitas Journal of Biological
Diversity. 7(4).
Prashanth D, Amit A, Samiulla D.S, Asha M.K, Padmaja R. 2001. Alpha
Glucosidase Inhibitor Activity of Mangifera Indica Bark. Fitoterapia.
72(6):686-8.
Sancheti S, Sancheti S and Seo S.Y. 2013. Antidiabetic and
antiacetylcholinesterase effects of ethyl acetate fraction of
Chaenomeles sinensis (Thouin) Koehne fruits in streptozotocin-
induced diabetic rats. Experimental and Toxicologic Pathology, 65(1),
55-60.
Scarano W.R, Messias A.G, Oliva S.U, Klinefelter G.R and Kempinas W.G.
2006. Sexual behaviour, sperm quantity and quality after short-therm
streptozotocin-induced hyperglycaemia in rats. International Journal
Andrology. 29: 482-488.
Stahl. 1973. Drug Analisis By Chromatography. Transleted by Kosasih
Padmawinata and Soediro L. ITB-Press. Bandung
Wagner H, Bladt and Zgainski. 1984. Plant Drug Analysis. 225. Transleted by
Th. A. Scott. Springer-Verlag. Berlin
Wild S.H, Roglic, G, Green A, Sicree R and King H. 2004. Global prevalence of
diabetes: estimates for the year 2000 and projections for 2030:
response to Rathman and Giani. Diabetes care, 27(10), 2569-2569.
Zanatta L, De Sousa E, Cazarolli L.H, Junior A.C, Pizzolatti M.G, Szpoganicz B &
Silva F.R.M.B. 2007. Effect of crude extract and fractions from Vitex
megapotamica leaves on hyperglycemia in alloxan-diabetic
rats. Journal of ethnopharmacology. 109(1): 151-155.
ABSTRACT
Glimepiride is a third-generation oral antidiabetic drug of sulfonylurea
group capable of lowering blood glucose levels with small hypoglycemia side
effects. However glimepiride including the Biopharmaceutical Classification
System (BCS) class II has a solubility practically insoluble in water so that the
effect on the dissolution rate and bioavailability. The efforts to increase the
solubility and dissolution rate of glimepiride by the method of formation of
inclusion complexes using betacyclodextrin compounds with co-grinding and
solvent evaporation technique in a 1:1, 1:2 and 2:1 mole ratio. Yield solids of
inclusion complexes glimepiride in betacyclodextrin in solubility test until it
reaches equilibrium at 37±5°C for 24 hours and the dissolution rate test
using USP II (paddle) with a stirring speed of 50 rotations per minute,
phosphate buffer pH 7.4 as medium, 900 mL at 37±5°C. The result of
solubility and dissolution rate which indicates the formation of inclusion
complexes of glimepiride-betacyclodextrin occurred in the 1:2 mole ratio, in
co-grinding and solvent evaporation techniques, characterized by increased
solubility and dissolution rate of glimepiride compared to pure glimepiride
and the physical mixture of both. However, significant effect on solvent
evaporation technique.
INTRODUCTION
Glimepiride is a third-generation oral antidiabetic drug of sulfonylurea
group capable of lowering blood glucose levels with small hypoglycemia side
effects. However glimepiride including the Biopharmaceutical Classification
System (BCS) class II has a solubility practically insoluble in water so that the
effect on the dissolution rate and bioavailability (Kawabata, et.al., 2011).
One effort to increase the solubility of GMP is by forming inclusion
complex using cyclodextrin derivative compound that is betacylodextrin
(BCD) which has hollow shape (toroidal) with the outside of the cavity is
hydrophilic so easily soluble in water and the inside is hydrophobic (Bekers
dkk., 1991).
BCD forms an inclusion complex by "capturing" drug molecules as a
guest into their sockets so as to alter the physicochemical properties of the
drug molecule particularly its solubility properties. The minimum
requirements that drug molecules must meet in order to form an inclusion
complex are the size and shape of the drug molecule entering or partially
entering into the BCD cavity and the inclusion complex formed is stabilized
by intermolecular forces, such as the van der Waals, hydrogen bonding,
hydrophobic interactions and high-energy water discharges (Frank, 1975,
Bekers dkk., 1991, Rajewski and Stella, 1996).
The successful formation of GMP inclusion complexes in BCD is seen
from the increase of GMP solubility by solubility testing conducted to reach
saturation condition and affect the percentage of GMP dissolved in unit time
by dissolution rate test.
Methods
Manufacture of GMP-BCD inclusion complexes
Co-grinding Technique
Each GMP and BCD material is weighed based on a 1:1, 1:2 and 2:1 mole
ratio. Then both are mixed and milled manually with mortar and stamper for
30 minutes. Solids are collected in a glass tube, then stored in a desiccator.
Solvent evaporation Technique
Each GMP and BCD material is weighed based on a 1:1, 1:2 and 2:1 mole
ratio. Then the GMP is dissolved in methanol while BCD is dissolved in
aquadest. Both solutions were homogenized at constant stirring at 500 rpm
for 24 hours. This mixture is allowed at room temperature to evaporate the
solvent until a solid is obtained. Then mashed with a mesh screen number
20, to obtain the inclusion complex powder collected in a glass tube and
stored in a desiccator.
Solubility Test
The GMP-BCD inclusion complex powder previously produced from co-
grinding and solvent evaporation techniques in 1:1, 1:2 and 2:1 ratio is
Selection of 1:1 mole ratio to see the ability to form inclusion complexes
between 1 mole of GMP with 1 mole of BCD to increase GMP solubility, 1:2
mole ratio to see the effect of BCD mole increase on GMP solubility and mole
ratio 2:1 to see the effect of decrease number of moles of BCD to GMP
solubility.
The formation of GMP-BCD inclusion complexes was performed by co-
grinding and solvent evaporation techniques.
Solubility Test
The results of solubility test of GMP-BCD inclusion complexes in the 1:1,
1:2 and 2:1 mole ratios were compared with pure GMP powder and the
physical mixture both reached equilibrium conditions at time 24 are in Table
2 (Higuchi, 1965).
% Drug Release
Time in min
GMP PM 1:1 1:2 2:1
5 12,88 40,07 29,22 29,23 19,51
10 21,23 44,07 37,98 42,23 21,11
15 23,00 45,71 42,24 43,08 27,87
20 24,79 46,99 44,25 47,40 31,25
30 27,74 49,43 45,12 52,15 36,97
40 32,74 50,36 47,55 54,27 37,77
50 38,10 52,84 49,61 57,94 42,03
60 44,67 59,49 58,73 65,50 49,79
% Drug Release
Time in min
GMP PM 1:1 1:2 2:1
5 12,88 59,22 59,23 70,07 49,51
10 21,23 67,98 72,23 74,07 51,11
15 23,00 72,24 73,08 75,71 57,87
20 24,79 74,25 76,99 77,40 61,25
30 27,74 75,12 79,43 82,15 66,97
40 32,74 77,55 80,36 84,27 67,77
50 38,10 79,61 82,84 87,94 72,03
60 44,67 88,73 89,49 95,50 79,79
CONCLUSION
Based on result of solubility and dissolution rate showing the inclusion
complexes of glimepiride-betacyclodextrin is in the mole ratio of 1:2 both co-
REFERENCES
Bekers, O., et.al., 1991, Cyclodextrin in Pharmaceutical Field, Drug Dev. Ind.
Pharm., 17 (11), 1503-1549.
Challa, R., Ahuja, A., Ali, J., Khar, and R.K., 2005, Cyclodextrin in drug delivery
: an updated review, AAPS PharmScitech, 6(2), E329-E357.
Chen HW, Lin AH, Chu HC, Li CC, Tsai CW, Chao CY, Wang CJ, Lii CK, Liu KL.
2011, Inhibition of TNF-α-induced inflammation by andrographolide
via down-regulation of the PI3K/Akt signaling pathway. J.Nat
Product. 74(11):2408-2413.
Colombo, I., Grassi, G., Grassi, M. (2009). Drug Mechanochemical Activation.
JPharmSci. 98(11): 3961-3986.
Frank, S.G., 1975, Inclusion Compounds, J.Pharm.Sci., 64(10), 1567.
Higuchi, T., and Connors, K.A., 1965, Advances in Analytical Chemistry and
Instrumentation, 4, 117, Interscience, New York.
Isadiartuti, Dewi, dkk., 2005, Pembentukan Kompleks Inklusi Fenobarbital
dengan Hidroksipropil-β-Siklodekstrin, Majalah Farmasi Indonesia
16(1), 28-37.
Kawabata, Y., Wada, K., Nakatani, M., Yamada, S., Onoue, S. (2011).
Formulation Design for Poorly Water-Soluble Drugs Based on
Biopharmaceutics Classification System: Basic Approaches and
Practical Applications. Int. J. Pharm. 420: 1-10.
Rajewski, R.A., and Stella, V.J., 1996, Pharmaceutical Application of
Cyclodextrine.2.In Vivo Drug Delivery, J.Pharm.Sci., 85(11), 1142-1169.
ABSTRACT
The development of antidiabetic treatment has been growing from
time to time, either with pharmacotherapy or herbal therapy using natural
ingredients to control blood sugar levels of patients and prevent diabetic
complications. Black sticky rice traditionally used as food in Bali (jaje bali) can
be an alternative treatment in diabetics. The highly dominant anthocyanin
contained in black glutinous rice is expected to improve the performance of
pancreatic beta cells in the production of insulin and increase the activity of
insulin work. The results showed that black sticky rice (Oryza sativa L.) dose
800 mg / Kg BW was effective for lowering blood glucose level. The
histopathology analysis on pancreatic β-pancreas cells can regenerate
pancreatic β-cells in alloxan induced diabetic white male rats (Rattus
norvegicus). Dose 800 mg / Kg BW is a dose that can regenerate the highest
β-cells of pancreas.
Key words: Diabetes mellitus, black sticky rice, anthocyanin
INTRODUCTION
Diabetes mellitus is a disease to watch out for, the prevalence of
diabetes for all age groups worldwide is estimated at 2.8% in 2000 and 4.4%
in 2030. The number of diabetics prevalence is 171 million in 2000 and 366
million in the year 2030. The latest data in 2015 shown by the Association of
Endocrinology (PERKENI) states that the number of diabetics in Indonesia has
reached 9.1 million people.
Different types of antidiabetic treatments have been used for
centuries to treat diabetes. The development of antidiabetic treatment has
progressed from time to time, either with pharmacotherapy or herbal
therapy using natural ingredients to control blood sugar levels of patients
and prevent complications of diabetes. Modern drugs used as antidiabetic
include insulin, sulfonylureas, biguanide and glitazon. The use of antidiabetic
drugs is often accompanied by adverse effects and toxicities such as nausea,
CONCLUSION
Black glutinous rice water extract (Oryza sativa L.) has an influence on
regeneration β-pancreatic cells in white mice (Rattus norvegicus) male with
alloxan induced. Dose 800mg / Kg BW is dose which is capable of
regenerating β-pancreatic cells best demonstrated by the amount of β-
pancreas as indicator, so the higher the dose given the more number of cells
β-pancreas.
Black rice glutinous rice extract (Oryza sativa L.) has an effectiveness in
increasing insulin activity by lowering blood sugar levels 2 hours post
prandial white rat (Rattus norvegicus) males who are diabetic. Dose 800 mg
/ Kg BW is a dose that can lower blood sugar levels, so the higher the dose
given the greater the decrease in blood sugar levels.
ACKNOWLEDGEMENT
I would like to thank the parties who helped carry out this research.
Thanks to Kemenristek Dikti who has funded this research. Chairman of
Saraswati Academy of Higher Research Institute of Saraswati Ni Made
Dharma Shantini for her support and Researcher I Gusti Agung Ayu Kusuma
Wardhani who always petrified the completion of this research.
REFERENCES
Amma, N.R. (2009). Efek Hipoglikemik Ekstrak daun Murbei (Morus
multicaulis) Terhadap Kadar Glukosa Darah Tikus DM. Tesis. Bogor:
Program Studi Gizi Masyarakat dan Sumberdaya Keluarga IPB.
Aru W Sudoyo, Stiyohadi bambang, Alwi idrus et all 2009 Buku Ajar Ilmu
Penyakit Dalam Jilid I Interna Publishing, 885
Ditjen Bina Farmasi dan Alkes. (2005). Pharmaceutical Care untuk penyakit
Diabetes Mellitus. Jakarta: Departemen Kesehatan RI. Halaman 9, 29,
30, 32, 39, 43
Parisnawan. 2015. Identifikasi Senyawa Antosianin dan Metabolit Sekunder
dari Ekstrak Etanol Beras Ketan Hitam (Oryza Sativa L.) dalam
Pemanfaatannya sebagai ALternatif Pengobatan Demam Berdarah
Dengue. AKademi Farmasi Saraswati Denpasar. Bali
Pocock, S. 2008. Clinical Trials: A Practical Approach. Chichester: John Wiley
& Sons. p. 128 – 129.
Ridwan, 2013. Etika Pemanfaatan Hewan Coba dalam Penelitian Kesehatan.
Sandhar, H.K., Kumar, B., Prasher, S., Tiwari, P., Salhan, M., Sharma, P., 2011.
A revie of Phytochesmitry and Pharmacology of Flavonoid.
International Pharmaceutica Sciencia. 1(1) : 25-4
ABSTRACT
Cr-glutamic complex suplementation was conducted in pre-clinical
study as the hypoglicemic nutraceutical on nicotinamide-streptozotocin
induced diabetic Wistar rats. Three groups were examined on the effect of
Cr-glu [Cr(µ-OH)(glu)(OH)2]2·6H2O] (glu= glutamic) at dose (50, 150 and 300
µg/day). The remain groups are control (+) with chromium picolinate (CrPic),
control (-) diabetic group (DM) and non diabetic control (non DM) and
control group by glibenclamide. The toxicity of the compound was examined
by the liver and kidney function test on SGOT/SGPT, ureum and creatinine
determination. The result showed that the SGOT/SGPT was increased until
the 7th day, but decrease after treatment in 14 days. There was no significant
differences between the start and the end of the treatment (p>0.05).The
result was also found on the kidney’s function by BUN and creatinine
measurement. Cr (III)- glutamic acid is potentially developed as nutraceutical
product in the management of type-2 diabetes mellitus.
Keywords : Cr(III)-glutamic acid, hypoglicemic nutraceutical, toxicity,
INTRODUCTION
Supplement or nutraceutical is a part of the management of diabetes.
Diet, exercise, oral hypoglycemic agents and insulin endogen are other kind
of this . Nutraceuticals (often referred to functional foods) are natural
bioactive or chemical compounds that have health promoting, disease
preventing or medicinal properties[1]. This research is a part of application of
inorganic nutraceutical, an inorganic compound or metal-containing
medicinal product with special purpose as antiperglicemic agent.
Metal complex or organo-metallic compound as trivalent chroium has
been used in medicine in the management of diabetes mellitus. Intake of
chromium (III) complex showed considerable reduction in the glucose level
[2]
. Chromium works as a Glucose tolerance factor, by the interaction with
the insulin and its receptors on the first step in the metabolism of glucose
entry into the cell, and facilitates the interaction of insulin with its receptor
on the cell surface [3][4]. Chromium increases insulin binding to cells, insulin
streptozotocin [13]. Streptozotocin was dissolved in citrate buffer (pH 4.5) and
nicotinamide was dissolved in NaCl 0.9%. Hyperglycemia was confirmed by
the elevated blood glucose levels at day 7 after injection. Blood sample was
collected from the eye vein. Measurement of blood glucose level was
conducted by using spectroscopic methods.
The Supplement in this work were synthesized in previous study[8]. The
formula is Cr-glutamate ([Cr(µ-OH)(glu)(OH)2]2·6H2O]). The supplement was
adiministered in 50,150 and 300 µg Cr/ day respectively, marked by Cr-AA1
(A), CrAA2 (B) and CrAA3 (C). The blood glucose level od diabetic subject is
126 mg/dL or more. Blood samples were taken and measured at H0
(start), H8 ( a week after induction) and H28 (4th week). The blood was
collected from the eye vein.
The acute and sub chronical toxicity and the function of hepar
The diabetic rats were administered with oral suppementation of Cr-
AA, by 300 µg/day. CMC-Na was given to the control group. The treatment of
these subject were carried out in 5 weeks. The acute and sub chronical
toxicity and the the function of the hepar were measured by the value of
SGOT/SGPT, ureum, and creatinine.
The 1 st pre clinical test showed the potent of Cr(III)-glu as
hypoglicemic agent to the stz- nicotinamide diabetic rats(17). The effect of
supplementation showed that Cr-Glu give a better histophatological
performance of proximal tubules compared to standard oral therapy with
glibenclamide. The Cr-Glu groups also have the less degeneration and
necrosis, although still have a small part of congestion and blooding. The
dose of Cr-Glu 150 by µg/day was not give a significant effect in the
regeneration of diabetic subject in this research. It is necessary to pay
attention to the dose 200-300 µg/day, for futher research. It is also
Table 2. The SGOT and SGPT value in acute supplementation of Cr-Glu (in
U/I)*
The increasing of SGOT and SGPT indicated the damage in the cells of
the hepar. The normal SGOT and SGPT value in wistar albino rat are 30,2-
45,7 U/I and 2,1-23,8 U/I, respectivelly. As showed in Table 2, the average of
SGOT and SGPT of the treatment group by Cr(III)-glu (300 µg/ day ) was
increased until the 7th day. Supplementation in 7 days later decreased the
SGOT level to the value of the normal condition (starting time). The SGPT
decreased until lower level than the begining (H0). Statisctical analysis by
Anova single factor showed that there is no difference between the SGOT
level between non induced subject and after supplementation. In the other
word, the are a significant effect of the supplementation of Cr(III) in acute
interval (14 days) (p>0.05).
Kidney is also a target organ in the investigation of the acute toxicity
of Cr(III)-glu supplementation.The pre-clinical test of acute toxicity in kidney
was determined in the Blood Urea Nitrogen / BUN) and creatinine. Ureum is
is the residue of the protein metabolism which is toxic in the body. It must be
excreted by the activity of the kidney in urine. The incresing of the ureum
indicated the disturbance of the kidney’s function. Creatinine is a product
of the decomposition of the creatine, which is syntesyzed in the hepar as
(creatin phosphate, CP), as an energy storege. In the usage of teh energy, the
process produced creatinine, which is filtered by the glomerulus in the
kidney and excreted as urine. The amount of ureum and creatinine were
used in the assesment of the kidney function. The measurement of BUN-
creatinine of the treatment subject in this research was listed in table 2.
Table 2 . Blood Urea Nirogen (BUN) and creatinine by acute Cr-Glu (mg/dl)*
Parameter (H0) (H8) (H14) P**
BUN 35.00±5.80 37.2±0.00 33.60±0.00 0.109
creatinine 0.20±0.05 0.29±0.00 0.34±0.00 0.604
*average ± SD **Anova single factor (p<0.05)
The normal value of BUN and creatinine of albino rats are 13.9 – 28.3
mg/dl and 0,30-1.00 mg/dl respectively. The result of BUN and creatinine in
Table 2 showed the difference in trend. The highest BUN is in the 7th day, but
the highest creatinine is at 7th day. The BUN level then decreased until the
lower value than the day before induction. Statistical analysis showed that
there was no significant difference of both the BUN and creatinine between
before and after diabetic induction. It means, the diabetic condition
increased the BUN and creatinine level according to the disturbance of
kidney activity, but after supplementation of Cr-III)-glu, they came back to
the normal level. The increasing of BUN and creatinine of the diabetic subject
in this research was not sufficient high. Overall, the kidney was normaly
work during the supplementation of Cr-glu (300 µg/day).
Sub-chronical toxicity aimed to know the effect of the supplement to
the subject. The interval is about 10% of the lifetime (about 1-3 month). The
investigation of sub chronical toxicity was carried out during
supplementantion of Cr-glu in 4 weeks (28 days). The result was showed in
Fig 1.
Fig. 1 indicated that Cr –glu tends to decerase the SGOT and SGPT
after increasing of both them according to the induction of diabetic by Stz-
nicotinamide. Sub-chronikal toxicity in kidney was observed by
determiantion of BUN) and creatinine until 28th day. The result showed in
Fig. 2 and Fig. 3.
intake. It means that the increasing of the value was not the one and only
indicator of the damage in the kidney. As found in the previous research on
the histopatological performace if the kidney, the supplementation of Cr- glu
(300 µg/day) was not affected to the hepatotoxic and neufrotoxic and the
activity of the hepar dan kidney[18]. In the other word, the supplementation
of Cr(III)-glu is safely recomended.
CONCLUSSION
Cr (glu) complex is potentially as nutraceutical product to type 2
diabetes mellitus. Toxicity of this product has been evaluated to acute and
sub chronical interval. The supplementation of Cr(III)-glu is safely
recommended until 300 µg/day in 28 days. Chronical toxicity was needed to
investigate the further effect in toxicity.
ACKNOWLEDGMENT :
The research was funded by The Ministry of Research and Higher
Education, by “Hibah Bersaing” research scheme.
REFFERENCES
[1] Pandey, M., Vijayakumar., 2011, Nutraceutical Supplementation for
Diabetes : a Review, Int. J. Pharm. Pharmaceutical Sci., 3 (4), 33-40.
[2] Z Krejpcio, Essentiality of Chromium for Human Nutrition and Health,
Pol.J, Environ. Studies, 2001, 10 (6) 399-404.
[3] JB Vincent, (ed), The Nutritional Biochemistry of Chromium(III),
Elsevier,New York, 2007 : 139-151.
[4] RA Anderson., Chromium and the Prevention and Control of Diabetes,
Diabetes & Metabolism, 2007,vol.26, p. 22-27.
[5] D Boghchi, SJ Stohs, BW Downs, Cytotoxicity and Oxidative Mechanism
of Different Forms of Chromium Toxicol, 2002, No. 180 (1), 5-22.
[6] Tawkir, M., & Iqbal S.A., Synthesis, Characterization and Medical
Efficacy of Cr(III) Complexes of Sulphonil ureas as Oral Antidiabetics,
2012, Asian J, Pharm and Clin. Res,5(4).
[7] E.Ochiai, Bioinorganic Chemistry, John Willey & Sons, New York. 2008,
p.235.
[8] K.S. Budiasih, C.Anwar, S.J.Santosa, H.Ismail, 2013, Synthesis and
Characterization of Chromium (III) Complexes with L-Glutamic Acid,
Glycine and L-Cysteine, Waset Journal, 78, pp 1095-1909.
[9] EU Etuk, 2010, Animals Models for Studying Diabetes Mellitus, Agric.
Bio. J. of. N. Am., 2010:1 (2), 130-134.
ABSTRACT
Patient satisfaction is an affective and dynamic reaction associated
with a feeling of comfort, friendliness, speed of service and the provision of
information about health needs. Based on data from hospitals Brigjend H.
Hasan Basry Pharmaceutical care field shows the SME (Society Satisfaction
Index) in 2013 amounted to 64.75 with good service quality, in 2014
amounted to 54.43 with poor quality of service and in 2015 amounted to
55.6 with poor service quality. It is known that pharmaceutical IKM is below
standard and is the lowest index in the field of medical service. The aim of
research to explain to explain the influence of pharmaceutical care with
patient satisfaction level outpatient Jamkesda program. This study uses a
quantitative method with observational analytic design with cross-sectional
approach. This study population is outpatient program Jamkesda (132
people), sampling using purposive sampling with research instruments such
as questionnaires. The results showed five dimensions of quality
pharmaceutical services that significantly affect Appearance Pharmacy (p-
value = 0.0001) and Drug Information Service (p-value = 0.009). The
conclusion from this study is there is an influence of the 2 dimensions of
quality pharmaceutical care to patient satisfaction. Advice can be given that
the hospital could multiply seat waiting room pharmacy and the pharmacist
may become clear drug information slowly and clearly.
Keywords: Appearance Pharmacy, Drug Information Service, Patient
Satisfaction
INTRODUCTION
Pharmacy Installation is one of the health service facilities that handles
the distribution of drugs to patients, pharmacy supply line directly to the
community and pharmacy as a place of pharmacy service. Pharmaceutical
services are health services that have an important role in realizing quality
The result of chi-square test with 95% confidence level, to see the
influence between appearance pharmacy installation to the satisfaction level
that p-value = 0,0001, from p value in statistical test result Ho decision was
rejected (p <0,05) which means there is a significant influence between the
appearance of pharmaceutical installation to the level of satisfaction means
the better the appearance of the pharmacy then the satisfaction of patients
using the services of pharmacies will be higher.
Based on the results of research from Ryu and Han (2010) comfort in
waiting is one of the factors that can affect patient satisfaction using the
services of pharmacies, and things that give comfort to the customer is an
attractive physical appearance and availability of supporting facilities, and
the appearance of a neat employee by using work uniform will give its own
characteristics as the image (image) about a service product that will be
given and sold to consumers.
CONCLUSION
Based on the result of the research, it can be seen that there is
influence between 5 dimension of pharmacy quality with patient satisfaction
level that is Pharmacy Appearance Appearance (p-value = 0.0001) anda Drug
Information Service -value = 0,009), The suggestions that can be given based
on the results of this study are: For the RSUD H. Hasan Basry Kandangan can
multiply the seats in the pharmacy waiting room so that patients can wait for
the medicine with relaxed and comfortable. For pharmacy installation
officers (pharmacies) can explain the drug information slowly and clearly, so
that patients can use drugs according to the rules.
ACKNOWLEDGEMENT
Many thanks to the RSUD Brig. H. Hasan Basry Kandangan who has
given permission in this research activity.
REFERENCES
1. Ifmaily. Analysis of the effect of perception of outpatient pharmacy service
service on the interest of drug buy back at RSI Pharmacy Installation.
Ibn Sina-Yarsi Padang Year 2006. Thesis. Semarang: Diponegoro
University, 2006.
ABSTRACT
Keto-acids are the nitrogen-free analogues of essential amino acids.
These amino acids therapy could be used as kidney protection by reduced
urea generation, delayed of uraemia and also reduced protein leaking into
urine. But there was a lack of study about the effectiveness of keto-acids
supplements in patients with Chronic Kidney Disease (CKD) in Indonesia. Aim
of this study is to evaluate the effect of keto-acid supplements on GFR
patients with CKD. A retrospective cohort study was conducted. Sixty two
patients with CKD divided into two groups. The trial group consist of 27
patients which treated by keto-acid supplements and the control group
consist of 35 patients without keto-acid supplements. The decrease of GFR
was measured in 3 month for CKD stage 5 and six month for CKD stage 4 and
3b. The decrease of GFR compared between two groups statistically using t-
test study. The results showed that there were no significant difference
between two groups baseline (p value gender = 0.64; p value age 0.74; p
value severity of CKD = 0.83). The decrease of GFR in trial group was lower
than in control group. In the trial group, the decreases of GFR in patient with
CKD stage 3b, 4 and 5 were -8.87±0.67, -4.11±2.29 and -1.40±1.03. While in
control group, the decrease of GFR value were -14.02±9.13 in stage 3b, -
4.47±4.45 in stage 4 and -1.60±1.01. But those difference in each stage of
patients were not statistically significant (p= 0.41 in stage 3b, p = 0.82 in
stage 4 and p= 0.72 in stage 5). We concluded that keto-acids supplement
has no significant effect on GFR patients with CKD in one of general hospital
in Jakarta.
Keywords: Keto-Acid, GFR, Chronic Kidney Disease, General Hospital, Jakarta
INTRODUCTION
Chronic Kidney Disease (CKD) is one of the high prevalence disease in
Indonesia. Indonesian Nephrology Association reported that the prevalence
in the hospital was not consistently measured every month, so there were
some gaps in data which affect the GFR measurement.
GFR Value
Stage p-value
Trial Group Control Group
3b -8.87±0.67 -14.02±9.13 0.41
4 -4.11±2.29 -4.47±4.45 0.82
5 -1.40±1.03 -1.60±1.01 0.72
CONCLUSION
We concluded that keto-acids supplement has no significant effect on
GFR patients with CKD in one of general hospital in Jakarta.
REFERENCES
Nitchwe. 2002. Dietary Protein Restriction in Chronic Renal Failure:
Nutritional Efficacy, Compliance, and Prognosis in Patient with Diabetic
Nephropathy. Kidney Int. 62: 220-28.
Bellizzi V. 2013. Low Protein Diet or Nutritional Therapy on Chronic Kidney
Disease. Blood Purif. 36: 41-46.
Garnaeta L, Mircscu G. 2013. Effect of Low Protein Diet Supplemented with
Keto Acid on Progression of Chronic Kidney Disease. J Renal Nutr. 23:
210-13.
Zemchenkov A, Konakova I N. 2016. Efficacy of the Essential Amino Acid and
Keto Analogues on the CKD Progression Rate in Real Practice in Russia
– City Nephrology Registry Data for Outpatient Clinic. BMC
Nephrology. 17: 62.
Kementerian Kesehatan Republik Indonesia. 2017. Situasi Penyakit Ginjal
Kronis. Jakarta: Pusat Data dan Informasi Kementerian Kesehatan RI.
Kementerian Kesehatan Republik Indonesia. 2013. Riset Kesehatan Dasar.
Jakarta: Kementerian Kesehatan Republik Indonesia.
Perkumpulan Nefrologi Indonesia. 2014. 7th Report of Indonesian Renal
Registry.
ABSTRACT
A Stroke is the leading cause of death and disability, stroke recovery in
order to achieve a good quality of life need to the role as well as patients,
families, health workers and the surrounding community are integrated. The
purpose of this research is to know the characteristics of patients and
measure the utility value of the EQ-5D-5L and VAS symptoms of ischemic
stroke in Bethesda hospital Yogyakarta. Analytic observational research
methods design of cross-sectional based on patient interviews. Purposive
sampling technique has taken samples. Research subjects who meet the
inclusion criteria of 48 patients with the characteristics of the age, gender,
education, age, and occupation. Criteria for Inclusion include patient JKN, the
ischemic stroke of the first offensive, onset of fewer than 24 hours and none
of the references. The period of observation for 1 month with interviews
directly outpatient and inpatient with 3-month reminder systems
retrospectively given the State of the patient's medical condition. Health-
related quality of life was measured using the EQ-5D-5L questionnaire and
vase. The data collected are presented in the form of tables and charts were
analyzed using t-test with a 95% confidence level. Based on the results of the
statistical tests of the characteristics of the status, age, education, gender,
work, there were no significant influence (p > 0.05) against the value of the
utility of the EQ-5D-5L and VAS. Health status of hemiparesis has the lowest
utility value 0.592 and also the lowest VAS 65.06. Health status the highest
utility 0.887 on stage health face weakness and the tallest VAS 80.40 on
stage health paresthesia. The value of the utilities the EQ-5D-5L and the
VAS is not affected by patient characteristics factors but factors comorbid
and other complications which affected it.
Key words: Utilities, EQ-5D-5L, VAS, Ischemic Stroke
INTRODUCTION
Stroke became the cause of death tersering third after heart disease
and cancer and ranks first as a cause of disability (World Health Organization,
2015). The stroke also occupied the highest mortality rate in Indonesia
according to Riskesdas 2013. Treatment of stroke due to disability and
recurrent stroke, discomfort and dissatisfaction costs high enough to handle
the situation (Riskesdas, 2013). The prevalence of stroke sufferers in Asia 50-
400 people per 100,000 population per year (Bethesda Stroke Center, 2007).
A stroke is a clinical syndrome with symptoms in the form of impaired
brain function in focal and global that can cause death or disability who
settled more than 24 hours without any other cause except vascular
disorders. While the ischemic stroke is a stroke caused by a blockage of the
arteries that supply blood to the brain suddenly (World Health Organization,
2006).
Stroke is the biggest cause of the inability of the physical, emotional,
and social life in adults (BÁRTLOVÁ et al., 2007). Although stroke is a disease
that attacks the central nervous system, the resulting effect can affect the
entire body. Effects that may occur include paralysis, cognitive function
deficits, difficulty talking, emotional difficulties, problems in daily life, as well
as pain (NINDS, 2007). Stroke also is closely associated with depression.
Depression usually appears in the first two years after someone affected by
stroke (Lynch et al., 2008).
The inability of the physical, emotional, and social life of stroke
patients of course affect its social role. It gives a great influence towards the
health-related quality of life in stroke patients (Shofri, 2016). Measuring
health-related quality of life in stroke patients became common with the
recognition that the evaluation of stroke patient care must include the
quality at the same time the quantity of survival of the patient. These
measurements usually include elements of functional, physical,
psychological, and social of the patients (Almborg and Berg, 2009).
Measuring health-related quality of life in stroke patients are not only to
know the reaction of the patient against his illness and enhancing the efforts
of supportive care, but also to evaluate therapies that have been done (de
Haan et al., 1993).
The measurement of the quality of life of stroke patients is
indispensable to know the severity of the condition symptoms of ischemic
stroke. The measurement of the value of the utiltas patients there are
several types of EQ-5 d Questionnaire covers-1.5 l jar, EQ-5 d-3 l, Barthel
Index (BI), Study the SF-36 and the value of the Modified Ranking Scale
(mRs). Health-related quality of life was measured using a questionnaire the
Medical Outcomes Study SF-36 (SF-36). Health-related quality of life scores
on ischemic stroke patients the first attack is higher than the recurrent
attacks of ischemic stroke patients (mean ± standard deviation, ± 2238 399.7
with 1596 ± 554.2, P = 0.001). Also obtained meaningful differences between
the average score on health-related quality of life dimensions of physical
function (62 ± 24.8 with 25 ± 15.8, P = 0000), the role of the physical (23 ±
19.9 with 3 ± 8.8, P = 0.007), energy (75 ± 17.2 with 52 ± 17.7, P = 0.001)
(Yani, 2010).
The incidence of recurrent stroke often occurs among patients who
have recovered from a stroke. About 25% of patients will experience
recurrent stroke occurrence. Risk of death and disability after stroke is
increased by the presence of recurrent stroke events (NINDS, 2007). An
increase in the risk of the inability also showed an increase in the risk of a
decline in the quality of life in stroke patients.
The importance of measuring health-related quality of life in patients
of ischemic stroke and an increase in the risk of ischemic stroke patient
inability the attacks repeated pushing researchers to conduct research so
that the risk factors trigger the onset of strokes can be avoided and the early
symptoms of this disease can be immediately detected. The handling of this
disease therapy as soon as possible which will meminimalis the level of
disability and death. The purpose of this research is to know the
characteristics of patients and measure the utility value of the EQ-5 d.5 l jar
VASE and symptoms of ischemic stroke in bethesda hospital yogyakarta.
Tabel 1. Utility value of the EQ-5D-5L and VAS Ischemic Stroke In Bethesda
Hospital Yogyakarta From 1 October 2015-30 September 2016
85
Muslimah
87
Muslimah
CONCLUSION
Based on the research results based on the characteristics of
education, age, married status, gender and pekerjaa there is a significant
influence (p < 0.05) against the value of the utility of the EQ-5D-5L and VAS.
The utility value of paralysis limbs (hemipharesis) has the lowest utility value
and also the lowest VASE 0.592 65.06. The most high utility value utility
0.887 on stage health face perot (facea weakness) and the tallest VAS 80.40
on stage health tingling (paresthesia). Quality of life of stroke patients in
addition to the many factors that affect the characteristics of the patients
are also factors of complications and komorbid.onclusion is a brief summary
of findings and discussion. It is strongly recommended to avoid mere
repetitive statements from the previous sections.
REFERENCES
Almborg, A., Berg, S., 2009. Quality of life among Swedish patients after
stroke: Psychometric evaluation of SF-36. J. Rehabil. Med. 41, 48–53.
doi:10.2340/16501977-0287
Bethesda Stroke Center, 2007. RS Bethesda Jadi RS Pelopor Stroke Center di
DIY - Tribun Jogja [WWW Document]. URL
http://jogja.tribunnews.com/2017/09/05/rs-bethesda-jadi-rs-pelopor-
stroke-center-di-diy (accessed 10.6.17).
de Haan, R. d, Aaronson, N., Limburg, M., Hewer, R.L., Van Crevel, H., 1993.
Measuring quality of life in stroke. Stroke 24, 320–327.
Karim, U.N., Lubis, E., 2017. Kualitas Hidup Pasien Stroke dalam Perawatan
Palliative Homecare. J. Ners Dan Kebidanan Indones. 5, 42.
doi:10.21927/jnki.2017.5(1).42-50
Lynch, E.B., Butt, Z., Heinemann, A., Victorson, D., Nowinski, C.J., Perez, L.,
Cella, D., 2008. A qualitative study of quality of life after stroke: the
importance of social relationships. J. Rehabil. Med. Off. J. UEMS Eur.
Board Phys. Rehabil. Med. 40. doi:10.2340/16501977-0203
NINDS, 2007. NINDS Know Stroke Campaign - Know Stroke Home [WWW
Document]. URL https://stroke.nih.gov/ (accessed 10.6.17).
Pattanaphesaj, J., Thavorncharoensap, M., Teerawattananon, Y., Tongsiri, S.,
2014. Health-related Quality of Life Measure (EQ-5D-5L):
Measurement Property Testing and Its Preference-based Score in Thai
Population. Mahidol University.
Shofri, 2016. Difference in Anxiety between Left and Right Hemispheric
Lesions of Ischemia among Patients with Stroke at Dr. Moewardi
Hospital | Shofri | Indonesian Journal of Medicine [WWW Document].
URL
http://www.theijmed.com/index.php?journal=theijmed&page=article
&op=view&path%5B%5D=24 (accessed 10.6.17).
World Health Organization (Ed.), 2006. Neurological disorders: public health
challenges. World Health Organization, Geneva.
Yani, F.I.A., 2010. Perbedaan skor kualitas hidup terkait kesehatan antara
pasien stroke iskemik serangan pertama dan berulang. Universitas
Sebelas Maret.