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ISSN: 2277- 7695

CODEN Code: PIHNBQ
ZDB-Number: 2663038-2
IC Journal No: 7725

Vol. 1 No. 7 2012
Online Available at www.thepharmajournal.com

THE PHARMA INNOVATION

Formulation and Evaluation of Buccal Patches of
Simvastatin by Using Different Polymers
Shalini Mishra1* , G. Kumar1, P. Kothiyal1

1. Division of pharmaceutical sciences, S.G.R.R.I.T.S. Patel Nagar, Dehradun, Uttarakhand-248001, India

The objective of this study was to develop mucoadhesive buccal tablets of Simvastatin using
mucoadhesive polymers. Simvastatin has short biological half-life (3hr), high first-pass
metabolism and poor oral bioavailability (5%), hence an ideal candidate for buccal delivery
system. From the present study carried out on simvastatin buccal patches prepared from 1%
eudragit-RS100 and variable amount of different polymer composite, PVP, PVA, HPMC and
EC. The buccal patches prepared using 50% glycerine w/w of polymer weight were found to
have good physical characteristics. The mean thickness of buccal polymeric patches increased
with an increase in the amount of polymer percent. Eudragit RS-100 HPMC (1:2) containing
50% glycerine w/w of polymer weight had is maximum thickness. Percent swelling index
determined at 5, 10, 30 and 60 minutes increased with time and with an increase in hydrophilic
polymer. Eudragit-RS100-HPMC buccal patches better swelling index, , folding endurance
followed by Eudragit-RS100-HPMC, Eudragit-RS100-PVA and Eudragit-RS100-PVP buccal
patches. . The increase in the amount of polymer retarded the release of simvastatin. F1
(eudragit-RS100-PVP) showed the maximum and faster release. Simvastatin was incorporated in
the selected polymeric patches and these were then evaluated for content uniformity and in vitro
release. Higher drug release was obtained.
Keyword: Buccal Mucosa, Transmucosal Drug Delivery, Buccal Patches, Simvastatin, Polymers, Bio
Adhesion, In Vitro release.

INTRODUCTION: Historically, the oral route The reasons for this preference are obvious
of drug administration has been the one used because of the ease of administration and
most for both conventional as well as novel drug widespread acceptance by patients. Major
delivery. limitations of oral route of drug administration
are Some drugs irritate the gastrointestinal tract
Corresponding Author’s Contact information: and this is partially counteracted by coating. Oral
Shalini Mishra * route may not be suitable for drugs targeted to
Department of Pharmaceutical Sciences, S.G.R.R.I.T.S., specific organs.The conventional type of buccal
Patel Nagar, Dehradun, India. dosage forms are buccal tablets, troches and
E-mail: diya.anacool@gmail.com
lozenges, and mouth washers. Amongst the

Vol. 1 No. 7 2012 www.thepharmajournal.com Page | 87

And other chemicals used the first pass hepatic metabolism leading to high were of analytical grade and produced from bioavailability.and UV-VIS spectrometric painless administration. The primary novel drug delivery systems. easy withdrawal. statins reduce tissue. Kothiyal various routes of administration tried so far in the name Zocor. the rate-limiting enzyme of the HMG- delivery by retaining the formulation in intimate CoA reductase pathway. facility methods to include permeation enhancer/ enzyme inhibitor or pH modifier in the formulation. Statins are more effective than other of a material (synthetic or biological) to adhere to lipid-regulating drugs at lowering LDL- a biological tissue for an extended period of time. disks. Simvastatin is a synthetic Glycerine (plasticizer) was then added to the derivate of a fermentation product of Aspergillus polymeric solution in the desired ratio 10 ml of terreus. pharmaceuticals. Required amount of eudragit RS 100 was then Simvastatin is a Hypolipidemic used to control dissolved in the solution. Concentrations of simvastatin were measured suitability for drugs or excipients that mildly and with a uv-vis spectrometer And polymers was reversibly damage or irritate the mucosa. the cardiovascular disease events and total mortality phenomenon is referred to as mucoadhesion. Methods versatility in designing as multidirectional or Preparation of polymeric solution:- unidirectional release system for local or Accurately weighed quantity of PVP was systemic action . exercise. In addition. localized drug uses of simvastatin is for the treatment of delivery to tissues of the oral cavity has been dyslipidemia and the prevention of cardiovascular investigated for the treatment of periodontal disease. lmtd.Shalini Mishra*. Well defined bioadhesion is the ability cholesterol. cholesterol concentration but they are less The biological surface can be epithelial tissue or effective than the fibrates in reducing triglyceride it can be the mucus coat on the surface of a concentration. methylglutaryl coenzyme A HMG-CoA within the gastrointestinal tract) or systemic reductase. the metabolic pathway contact with the absorption site (e. buccal patch offer greater flexibility and comfort than the other MATERIALS AND METHOD :- devices. 7 2012 www. The drug is marketed under the trade the resultant Vol. It is recommended to be used only after disease.g. Kumar.[3] dispersed in 5% ethanol aqueous solution. since the gels are easily pharmaceutical pvt. protein binding is 95%. strips.thepharmajournal.[4. potential to optimize localized drug delivery. as well as generically. 1 No.com Page | 88 . have recently been developed. verified using FTIR. ointments and gels. The irrespective of the initial cholesterol use of mucoadhesive polymers in buccal drug concentration. including tablets. bacterial and fungal infection.Chandigarh (India) washed away by saliva. However. a patch can circumvent the Materials:- problem of the relatively short residence time of Simvastatin was a gift sample from Ind swift oral gels on mucosa. Buccal route of drug Hydroxy propyl methyl cellulose. It was then kept for 24 hours in a sonicator and is a member of the Statin class of then it was filtered through a muslin cloth.5] patches. P. The t1/2 for simvastatin is 2 to 4 delivery has a greater application. or hypercholesterolemia. films. Ltd. This polymeric solution elevated cholesterol.g. However. Over the other measures such as diet. low enzymatic activity.Ethyl cellulose delivery provides the direct access to the systemic and Eudragit RS 100 were obtained from Central circulation through the jugular vein bypassing drug house pvt. If adhesion is to a mucous coat. and weight decades mucoadhesion has become popular for its reduction have not improved cholesterol levels. by All statins act by inhibiting 3-hydroxy-3- retaining a dosage form at the site of action (e. G.India) excellent accessibility. Various hrs and bioavailablity is 5% and efficiency of mucoadhesive devices. buccal responsible for the endogenous production of cavity)[1]. Other advantages such as central drug house (New Delhi.

The solution was measured against the corresponding glycerine was used as plasticizer in percent of blank solution at 248 nm. was poured into the Thickness uniformity of the patches[6]:. Adamulthomargy. petridish. Weight Calculated amount of simvastatin (30 mg/cm²) increase due to swelling: A drug-loaded patch of was dispersed in the polymeric solution. swelling. 1 No.1 N cm. The difference in the oven at 45ºC for 24 hours. eudragit.. after the 1x1 cm2 was weighed on a preweighed cover drug is completely dispersed. volumetric flask (10 ml). was calculated using the following equation: Folding endurance[7]:- Folding endurance of the patches was determined (Khanna et al. 30% and 50% w/w of polymer weight. G. Ten ml of a 0. The contents were transferred to a out for the preparation of eudragit-PVA. Vol.2 placed in a beaker.weighed upto 30 min. A graph paper was placed beneath the petridish. 7 2012 www. Kumar.Shalini Mishra*. The patches obtained were used as such or hydrochloric acid solution was added. The absorbance of the HPMC. EVALUATION OF BUCCAL PATCHES: to measure the increase in the area.6.Area paper in a dessicator. pH 6.6 was added. The dispersion was casted five min. Tensile strength of the patch was determined with Digital Tensile Tester (DY-20. Kothiyal mixture was poured into each fabricated glass Drug content uniformity of the patches[8]:- ring placed on a mercury substrate. It was kept in a petridish and 50 ml of (plasticizer) was added and stirred to form a phosphate buffer. number of times of patch could be folded at the same place without breaking gave the value of the folding endurance. The patches thus weights gives the weight increase due to formed were removed and stored between butter absorption of water and swelling of patch. %S. A patch of size 1×1 cm2 was cut and resultant polymeric patches had a diameter of 6. An increase in the length and breadth of The thickness of each patch was measured using screw the patch was noted at five min intervals for 60 gauge at five different positions of the patch and the min and the area was calculated. eudragit-EC polymeric patches.thepharmajournal. After every uniform dispersion. Drying was The patches were tested for the content carried out at 45ºC for 24 hours in hot air oven. The weight or area at zero time. Similar procedure was carried the film. The percent average was calculated. 1995). uniformity.com Page | 89 . pH 6. 20%. Fifty ml of phosphate buffer. 1997) by repeatedly folding one patch at the same place till it broke or folded upto where Xt is the weight or area of the swollen 300 times manually. the cover slip was removed and onto the mercury substrates kept in the hot air. glycerine slip. increase due to swelling: A drug loaded patch size of 1x1 cm2 was cut and placed in a petridish. P. which was considered patch after time t and Xo is the original patch satisfactory to reveal good patch properties. France 1986). The cut into a diameter of 1 cm² for different contents were stirred in a cyclo-mixer to dissolve evaluation studies.:- Swelling studies of the patches[9]] Weight and area increase due to swelling were Method of Preparation: measured (Gua and Cooklock. This test was done on five Tensile strength of the patches[10]:- patches.

80 50.5224 6.89 23. . .256 105.89 54.com Page | 90 . .78 2. .118 F7 0. .97 1. . . . . .54 1.18 1.8568 F4 0.89 53.3585 155. . - EC . - PVA .88 0. Kumar. .390 16 7. . .Shalini Mishra*.12 19. .5% 2% .67 34. . 1 No.128 F10 0.3565 132. 1% 1.64 33.5223 7.88 0. 7 2012 www. G. .5242 10.74 2.35 0. 1% 1. . .80 31.68 9. .0 1.4168 F2 0.5209 5.47 28.5225 3.55 0.3686 162.55 0.49 1. .63 23.06 27.34488 125.7068 F3 0.5231 12.98 44.87 23. Kothiyal Table No:1 : Composition of different buccal mucoadhesive formulations containing Simvastatin Ingridient F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12 Simvastatin(mg) 20 20 20 20 20 20 20 20 20 20 20 20 Eddragit RS-100 1% 1% 1% 1% 1% 1% 1% 1% 1% 1% 1% 1% PVP 1% 1.5215 8.77 13.220 96.227 104.30 37.9635 F9 0.88 24.57 9.89 44.37 27.5231 5.60 39.5% 2% .80 19.35 0.94 12.69 2. 1% 1.2968 109.291 106.96 27.49 18. .46 42. .047 F6 0. .16 17.889 F8 0.68 2.26 F12 0. . P.80 0.70 2.45 9.5242 8.83 22. . .00 0.68 2.5254 6.46 1.495 Vol.55 24.9368 F5 0.5250 15.80 44.00 0.5217 3.thepharmajournal.00 0.88 0.85 33.70 45.5% 2% Ethanol 5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5% 5% Glycerine(percent 50 50 50 50 50 50 50 50 50 50 50 50 w/w of polymeric weight) Table 2: Characteristics of buccal mucoadhesive patches containing Simvastatin Formulation Thickness Folding Content Percentage swelling index in time Tensile code endurance uniformity (min) strength (mm) (mg) 5 10 30 60 F1 0.10 13.5% 2% .2048 96.3295 115.49 22.65 34.1935 F11 0. - HPMC .00 0.

The lower one was fixed and upper one was movable. Five Eudragit RS-100 HPMC (1:2) containing 50% ml of the buffer was replaced immediately and glycerine w/w of polymer weight had is the beaker was kept covered with a petridish to maximum thickness. 7 2012 www. 0.8924 between these cell grips and force was gradually 0. PVA. Beer’s law obeyed from eudragit-RS100-PVP patches followed by to construct the calibration curve was in the eudragit-RS100 -PVA. The tensile strength of 0. P. A non.2 A patch of 1x1 cm2 size was cut and attached to a 0. PVP. whose tip was attached buccal polymeric patches increased with an to a tube with glass wool (as a filter). Kumar.Shalini Mishra*.427 Linear In vitro release studies of simvastatin patches (Series1) 0. D8 hrs 99. Kothiyal The sensitivity range of the machine is 1 to 10 Figure no:1 Calibration curve of Simvastatin Newtons. 1974).2735 in phosphate buffer (pH 7. Eudragit-RS100-HPMC buccal patches studies were conducted for three times and better swelling index.2) solution. Japan).5913 Series1 kilograms.7 hours. Eudragit- RS100-PVA and Eudragit-RS100-PVP buccal RESULTS AND DISCUSSION patches. 30 and 60 minutes increased were taken after every 10 min upto 90 min. Higher drug release was obtained Corporation. was quickly reintroduced into the beaker.com Page | 91 . In vitro release characteristics of Simvastatin buccal patches showed Vol.7 the patch was taken directly from the dial Absorbance reading in Newtons. The release polymer.95%.9869 applied till the film broke.in fig 2.3 0. 1 The test patch of size (5×3 cm2) was fixed 0. The buccal withdrawn periodically after removing the slide patches prepared using 50% glycerin w/w of from the beaker.6 0. 10. Tokyo. which was converted into 0.eudragit-RS100. Calibration curve of simvastatin in 0. The beaker was kept in circulating water bath in which the From the present study carried out on simvastatin temperature was maintained at 37oC.2) solutions were selected polymeric patches and these were then obtained at λmax 238 nm with a UV-VIS evaluated for content uniformity and in vitro spectrometer (UV-1601PC.2).7392 0. 1 No. eudragit-RS100 -HPMC concentration range of 2-10 μg/ml. G.8 R² = 0.057 0.EC F1 (chitosan-PVP 1:1) done in triplicate which shown in fig 1. This slide was kept at an angle of 45 o 0 0 in a 250 ml beaker containing 100 ml of 0 5 10 15 concentration(mg/ml) phosphate buffer (pH 7. Percent swelling index prevent evaporation of the fluid. Samples were following points can be concluded.1 N HCl and Simvastatin was incorporated in the phosphate buffer (pH 7.thepharmajournal.9 y = 0.2)[11]:. 0. HPMC and EC the (Borodkin and Tucker. buccal patches prepared from 1% eudragit-RS100 agitated system was selected to eliminate any and variable amount of different polymer effect of turbulence on the release rate composite. It consisted of two load cell grips. Shimadzu release. The mean thickness of using a graduated pipette. and with time and with an increase in hydrophilic analyzed for drug content at 238 nm.1 glass slide with a few drops of phosphate buffer (pH 7. folding endurance average was determined. The solution was stirred with a polymer weight were found to have good glass rod and 5 ml of sample was withdrawn physical characteristics. The slide increase in the amount of polymer percent. followed by Eudragit-RS100-HPMC.4 0. Analyses were and . The samples determined at 5.5 0. showed the maximum and fastest release t50% 1.086x + 0.

buccal patches prepared using 50% propylene glycol w/w of polymer weight were found to 11. Kavimani S. 7 2012 www.V. Agrawal SP and Alka Ahuja.D. Muhammed Ashereff MH.D.. www.236-55 F6 40 2.6% in 8 evaluation of propranalol hydrochloride buccal films”. eudragit-RS100-HPMC and eudragit- RS100-EC showed relatively retarded release 8. 2009. Saisivam S. F3 80 F4 REFERENCE: 1..Ist Ed..pno-417-54 20 F8 F9 3. HPMC and EC 10.K.pageno-573-578 decrease in percent release with an increase in the amount of polymer.fifth edition. PVA. 30 and 60 minutes increased Vol. Preparation and evaluation of mucoadhesive buccal films of have good physical characteristics. Eudragit-RS100-EC (1:2) containing 50% glyecrine w/w of polymer weight had is maximum thickness.jaypee prakashan.2 hours). simvastatin buccal patches The maximum 7. the least t50% 1. et al. G. Sankar. P.Tripathi. Kumar. Rajasekaran. 2001.7 hours was observed for F1 Indian Journal of Pharmaceutical Sciences 2000.From the present study carried out 9.com Page | 92 .N.Vyas. Khanna R.New Delhi..Ist Eds.Jain. & Khar. Zocor (Merck & Co) product monograph copyright 2001. one may conclude that these polymer systems of eudragit-RS100 along with 120 F1 PVP.S. Bioadhesive dosage form for release of 99. American the following points can be concluded. Indian Journal of thickness of buccal polymeric patches increased Pharmaceutical Sciences 1997. New Delhi. PVA).thepharmajournal.. ASTMD 882-80a. The National Standard.2002. Raghuraman. 0 5 10 TIME (HRS) F11 4.H. PVP. 1989. polymer composite. Mullaicharan AR.S. Mucoadhesive bilayered patches for 0 administration of sumatriptan. “Controlled Novel Drug Delivery”.P.6 hours) Rajan. Ilango R. 59(6): 299-6. In on simvastatin buccal patches prepared from 1% vitro studies on buccal strips of glibenclamide using chitosan. Jayaprakash S and Nagaranjan M. O’Neil CT.. evaluation of diltiazem hydrochloride buccal patches. Denito Johnson. Pharma Acta RS100-PVP) followed by F5 (eudragit-RS100. Helv.CBS 60 F5 Publishers and Distributors. with an increase in the amount of polymer percent. AAPS pharm sci tech.wikipedia. The mean clotrimazole for oral candida infections. Shidhaye SS. Thus. HPMC and EC have potential for consideration for drug delivery as buccal dosage 100 F2 forms.Deasy PB. Maria Gerald NS.2005. F10 9(3). “Targeted and Controlled Drug F7 Delivery Novel Carrier System”. Kothiyal Figure no-2 Percentage cumulative drug release of with time and with an increase in hydrophilic various formulations of simvastatin by using different polymers:- polymer.95% was observed for F1 (eudragit. Conclusion:.Shalini Mishra*. Percent swelling index determined at 5.com. “Design and with the least release observed for F12 54. Ravichandran.5 hours) and F11 (6. 10. CBS Publishers and Distributors. Design and followed by F9 (6.T.S. hours.pno. American Society for Testing of Materials. Eastern Pharmacist.Essentials of medical pharmacology. PVA. peroral administration of simvastatin base. 236-2. Indian Journal of Pharmaceutical Sciences 1997.2002. Jayakar B. 1 No.K. Eudragit-RS100 and variable amount of different 59(5): 232-3.2007 5. required for 50% of release 6. 109-111.V. Shaffia.. 64(8): 231-5.81. 1980: 380-388. was found to be maximum for F12 (7.