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Dr Ehsan Khan Nursing (adult & paediatrics)

Adult Nursing
Formulations

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Learning outcomes
• By the end of the session, you be able to:
• Appreciate the basic process required to take a drug from development to market
• Describe a range of different drug forms
• Differentiate between active drug and a range of excipients
• Provide an understanding of the risks of changing the formulation of a medication.

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 Pharmacology timeline

• 1809 François Magendie studied the action of nux vomica (a strychnine-

containing tree drug) on dogs
• 1828 Synthetic organic chemistry was born
• 1842 Claude Bernard discovered that the arrow poison curare acts at the
neuromuscular junction
• 1847, Rudolf Buchheim was appointed professor of pharmacology at the
University of Dorpat in Estonia (then a part of Russia). Birth of Pharmacology
• 1838–1921 Oswald Schmiedeberg founder of modern pharmacology
• 1897-1926 John J Abel Isolated adrenaline and crystalline pure insulin
• 1950 George Brownlee first Professor of Pharmacology at King's College.

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 Drug development

10,000 drug candidates

Pre-clinical studies

Clinical trials 10 drugs

Approved drug
1

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Phase 1 Clinical trials
• First examination of drug candidate in healthy humans
• Determine if the effects of the drug are similar to those observed in animal testing
• Determine the correct human dose of a drug
• Identify acute adverse side effects of drug

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Phase II Clinical Trials
• Drug used on selected patients to determine its effect on the disease it was designed to treat
• Therapeutic and adverse effect is examined

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Phase III clinical trials

• Drug entered into large clinical trial

• Effect of candidate drug compared against standard therapeutic treatments
• If drug is shown to be therapeutically effective and safe, then it is licensed by
the Medicines and Medicines and Healthcare products Regulatory Agency
(MHRA)

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Phase IV clinical trials
• Surveillance of the licensed drug continues.
• Long term effects especially of safety are evaluated
• Real clinical value of drug determined

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 Cost of Drug development (R&D + Production)

2.6

2.5

2
Billion ($)

1.5

1.2

1
0.802

0.5
0.318
0.231

0
1987 2000 2001 2006 2016
Data Source: http://csdd.tufts.edu/research-milestones
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Pharmacology
• Patent for new drug: 20 years
• 10 years for development
• 10 years to sell

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What is formulation?

Formulation is the process by which the active ingredient

in a medication (the drug) is combined with other
ingredients to form the final medicinal product.

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 Why worry about formulation
The form of drug is being changed
every day. But what are the
consequences.

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Considerations that govern formulation

Patient
Illness
Comorbidities

Therapeutic Drug
Bioavailability Stability
Clinical efficacy Shelf life
Patient
Preference

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Selected Drug forms
Capsules

Tablets
Compressed, multiple compressed, chewable, dispersible, sugar coated, film coated, gelatine coated
(Gelpcaps), buccal or sublingual, dispersible or effervescent, enteric coated.

Extended release preparation, e.g. multi-unit pellet release (MUPs)

Liquids
Monophasic (Solutions, Syrups, Elixirs, Linctuses). Polyphasic (Suspension, Emulsions Collodions)

Semi solid
Creams, gels Ointments, pastes
Inhalation
Patches
Aerosol
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Medication = Active drug + Excipients
• Excipients:- constituents of the medication that are administered or taken by the patient other than the
active drug substance.

Excipient (Example) Use

Binder (Gelatin)
Diluents (Dextrin/glucose) (silicate/calcium salts)
Disintegrants (Starch/alginates)
Glidants (silica compounds)
Preservatives (Alcohol/benzoic acid)
Coatings (Cellulose)
Binds to give form and strength to tablet/capsule
Provide bulk
Swell up in water and aid dispersion of drug in GI tract
Aid in fluidity of powders during manufacture
Antimicrobial activity/ may also act as solvents
Aid in swallowing, mask taste and odour, may delay
disintegration, environmental protection.

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Adverse effects of excipients
• Excipients in isolation may have adverse effects.
• Changing formulation of medication may remove culprit excipient

Excipient Common adverse effect

Benzalkonium chloride Bronchospasm (nebuliser solutions)

(preservative)
Lanolin (emulsifier) Hypersensitivity reactions (skin)

Propyl gallate (antioxidant) Sensitivity reactions (skin)

Sesame oil (solvent (injections) Hyersensitivity reactions

Tartrazine (colouring agent) Hyersensitivity reactions

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Medications that should not be crushed
• Any drug with m/r, LA, SA, CR, XL, SR or Retard or Slow found in the title): Leads to increased effect (toxicity)

• Enteric coated tablets; ( have EN, EC or FC in their title) Leads to loss of stability of medication in stomach acid.

• Hormonal preparations (cytotoxic steroids) e.g. tamoxifen: can be absorbed by nurse administering the
medication and cause them harm

• Nitrates: potential explosion risk.

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 Ruszikova et al (2015)
Quantitative analysis of drug losses administered via nasogastric tube – In vitro study https://doi.org/10.1016/j.ijpharm.2014.11.065

Mean losses associated with

(crushing, transfer, flushing) of drug
administration via NGT
(crushing–beaker–syringe–water–NGT).

Types of dosage forms:

T/S – simple compressed tablet,
T/EC – enteric coated tablet,
T/FC – simple film coated tablet,
C/ER – capsule containing extended release
pellets,
C/GR – capsule containing gastro-resistant
pellets.

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Tablet splitting

In addition to tablets already mentioned. Some tablets may crumble significantly on splitting
Helmy S (2015)
examined an selection of tablet, a number failed to split into equal half (in red).
• mirtazapine 30 mg, bromazepam 3 mg, oxcarbazepin 150 mg, sertraline 50 mg
• carvedilol 25 mg, bisoprolol fumarate 10 mg, losartan 50 mg, digoxin 0.25 mg, amiodarone HCl 200 mg
metformin HCl 1,000 mg, glimepiride 4 mg
• montelukast 10 mg, ibuprofen 600 mg, celecoxib 200 mg, meloxicam 15 mg
• sildenafil citrate 50 mg

DD/Month/YYYY Professor/Dr: Topic title: Helmy S, (2015) https://doi.org/10.18553/jmcp.2015.21.1.76

Tablet splitting

Nidanapu et al. (2016) examined Phenytoin sodium [PHE], sodium valproate [SVA], carbamazepine, and
phenobarbitone in paediatric patients
1098 split tablet parts:-
539 (49.0 %) split parts were above the specified limit
253 split parts were outside the acceptable content uniformity range of <85 %

130 (72.2 %) patients (Paediatric) had plasma drug concentrations outside the therapeutic range
(PHE 36 [72.0 %], SVA 39 [78.0 %], carbamazepine 34 [68.0 %], phenobarbitone 21 [70.0 %]).

Nadanapu et al , (2016) https://doi.org/10.1007/s40272-016-0193-1

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 Tablet splitting

Abu-Geras et al (2017) examined use of hand and tablet splitter techniques to divide tablets.
88 Participants
Tablet splitter was more accurate
>25% scored small tablets did not divide into equal halves
41% of large unscored tablets broke into > 2 parts with a tablet splitter

Aoki et al., 2021 examined dispersion of cytotoxic Azothioprine when being split, they recommend that
(1) (1) AZA tablet splitting should be performed while wearing gloves,
(2) (2) the gloves should be changed before packaging the half tablets
(3) (3) the tools, packaging machines, and dispensing counters should be wiped twice or thrice with a water-
dampened cloth after dispensing.

Abu-Geras et al (2017) https://doi.org/10.1111/jphp.12671

Aoki et al., (2021) https://doi.org/10.1248/yakushi.20-00106
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Summary
• Developing medication is an expensive prolonged process, allowing companies limited time to recoup
their investment before they lose patent.
• Multiple formulations of a medication are required to ensure safe and appropriate drug dosage.
• Different drug formulations have different delivery characteristics meaning that drug dosses are not
interchangeable between formulations
• Changing the form of the medication should be done with care and permission of the prescriber.
• Tablet splitting where allowed should be performed with a tablet splitter
• Solid forms of medication should not as a rule be crushed or opened and delivered via an NG tube, unless
written permission is provided by the prescriber and been verified by the pharmacist.

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