Running head: DRUG FORMULATION & PERFORMANCE 1

The impact of drug formulation on the drug performance

Khadejah Stewart

University of the West Indies, Mona

DRUG FORMULATION & PERFORMANCE 2

Abstract
The act of combining chemical substances to form a medicinal product with the inclusion of

an active drug is often referred to as drug formulation. In this process, the use of technology,

as well as varying methodologies, allows active drug substances to be released from their

medicinal product in various ways. These varied drug formulations affect absorption in the

body upon release of its active drug substance, its drug performance. A variety in treatment

regimens, instituted by health professionals, can be due to the many drug

formulations present on the drug market. This variety in therapy may be due to the

desired therapeutic effect, pharmacokinetics of the drug, as well as the preference of

the patient. Allowing for greater patient compliance as therapy is one which is, in most

cases, favoured by the patient. which in turn influences efficacy. However, it is not in all

cases, that the favoured outcome of the implementation of technology in drug formulation

produce favourable outcome.

Key words: drug formulation, drug performance, compliance, efficacy, technology, treatment

regimen
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Acknowledgement

I would like to thank Dr. Valerie Kerr for equipping me with the basic knowledge of research

methodology and biostatistics. As well as Dr. Maxine Gossell-Williams for providing

resources that aided in the formulation of the literature review and article critique.

I would also like to thank my colleagues who were willing to help me in the formulation of

the literature review.

DRUG FORMULATION & PERFORMANCE 4

The act of combining chemical substances to form a medicinal product with the

inclusion of an active drug is often referred to as drug formulation. In this process, the use of

technology, as well as varying methodologies, allows active drug substances to be released

from their medicinal product in various ways. These varied drug formulations affect absorption

in the body upon release of its active drug substance, its drug performance. This, in turn, leads

to the bioavailability of the drug substance. Technologies such as extended release to drug

encapsulation or the addition of a preservative to the final drug product have led to many studies

being conducted. These studies are set about to assess the effect the different formulations have

on therapy in patients of Caucasian, African and Hispanic descent. From the studies being

reviewed, different drug formulations have allowed for varied treatment regimens and have

influenced patient compliance and efficacy.

A variety in regimens, instituted by health profession als, can be due to the many

drug formulations present on the drug market. A regimen is a systematic therapy

designed to improve and maintain the health of a patient (“Regimen”, 2018). This

systemic therapy may be due to the desired therapeutic effect, pharmacokinetics of the

drug, as well as the preference of the patient. On the basis of desired therapeutic effect,

Derosa, Dangelo, Romano, and Maffioli (2017) in their randomized clinical study

highlighted this as the metformin immediate release (IR) taken t hree times daily at

doses of 500 mg, 850 mg or 1000 mg as a means of glycol-metabolic control. Whereas

the extended release (XR) formulation is taken once daily and provides the same

effect. With the introduction of extended-release technology, the plasma-drug

concentration is higher over a longer period maintaining the effective therapeutic

concentration. This causes an extend which uses a decrease in dosing as highlighted

in the study by Derosa et al. (2017) with the XR as opposed to the IR. However, the

study did not give the specific dose of XR that was used and did not stick to just one
DRUG FORMULATION & PERFORMANCE 5

dose of the IR which poses a limitation as it regards to the paper’s reliability. Damle,

Kaul, Behr, and Knupp (2002) in their open-label, randomized, two-way crossover

study of bioequivalence, a pharmacokinetic drug property, on didanosine; a varied

regimen was used where two of four groups received two 200 mg buffered tablets with

antacids. And the remaining two groups, a 400 mg encapsulated enteric -coated (EC)

beads. Additionally, the use of the encapsulated EC beads allows for the concomitant

administration of drugs that are affected by antacids. In turn, giving a wide scope of

treatment options, while performing the same drug effect in the body.

Consequently, varied regimens allow for greater patient compliance as a result of

decreased dosage frequency and dose quantity. Damle et al. (2002) shows this with the

encapsulated EC beads, stating that compliance was increased. As only one capsule had to be

taken instead of the buffered tablet and antacid, showing a decrease in dose quantity. For

didanosine is an antiretroviral drug that is given in a combination therapy consisting of other

antiretroviral agents. Similarly, metformin XR was observed to cause compliance as there was

a decrease in dosage frequency from three times daily as with the IR to just once daily with the

XR (Derosa et al., 2017). Abokyi, Ilechie, Boateng, and Koffuor (2016) note in their study that

the addition of the preservative benzalkonium chloride (BAK) to timolol decreases tear

instability as opposed to only BAK. Therefore, compliance is strengthened as the risk of dry

eyes is reduced due to the tear film instability decrease. In the case of children, compliance is

influenced by the palatability of the medicinal drug. As in the study by Cohen, Rocque,

Lécuyer, Wollner, Bodin, and Wollner, (2008) it was seen where 10 of the 879 cases assessed

had poor compliance due to taste. However, it is not every improvement in drug formulation

that leads to greater drug compliance. As further down in the literature by Damle et al. (2002),

it is noted that the buffered tablet regimen may be preferred as it poses less adverse events

(AEs). As the for the HIV infected subjects, three (3) AEs were seen in three (3) subjects on
DRUG FORMULATION & PERFORMANCE 6

the buffered tablet and five (5) AEs in two (2) subjects on the encapsulated EC bead

formulation. But with there being bioequivalence between the buffered tablet and encapsulated

EC beads the choice of therapy is solely based on the preference of the patient. For preference

is a factor that affects compliance, seen mostly with generics. As generics gives the allowance

for excipient variation which may cause the drug to be more acceptable or less. Cohen et al.

(2008) also noted that the amoxicillin clavulanic acid princep was favoured over the generic as

respective mean scores, based on taste, 3.3 and 2.98 were recorded. Which led to children

taking the princep more readily and complying to the treatment regimen stipulated.

Amidst compliance arises efficacy in treatment regimen as compliance is a key

component in ensuring a desired result is attained. As when the palatability of oral liquid

antibiotics is satisfactory to children, there will be less incidence of a child spitting out the

antibiotic. Thereby maximising the therapeutic outcome as a decrease in the risk of microbial

resistance is seen with a decrease in treatment failure risks (Cohen et al., 2008). Likewise,

patients are more compliant using the eye drops with timolol and BAK as the preservative in

their treatment regimen. As such, the effective treatment of glaucoma is increased for the risk

of dry eyes is decreased with the decrease in tear film instability (Abokyi et al., 2008). Also,

the glyco-metabolic control of patients with type 2 diabetes proved efficacious with the

metformin XR (Dereosa et al., 2017). Though drug formulation technology was implemented

for the didanosine, due to there being a bioequivalence between both formulations, the efficacy

difference was not considered to be significant.

In concluding, the literatures reviewed for the most part had similar themes portrayed.

As it was seen that the impact of drug formulation on its performance may be due to the variety

of treatment regimens now made available. As well as the fact that compliance and efficacy

are affected. Gaps in the literatures caused incoherent analysis, as seen with the work by Derosa

et al. (2017) where the succinct introduction did not give readers a good background on the
DRUG FORMULATION & PERFORMANCE 7

study being conducted. Likewise, for Cohen et al. (2008) the introduction did not define all the

terms clearly, and compliance and its relationship with therapeutic failures was also lacking.

Therefore, not validating the main driving force behind the study of how the taste acceptance

made a difference.
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References
Abokyi, S., Ilechie, A., Boateng, G., & Koffuor, G. (2016). Effect of preserved and preservative-

free timolol eye drops on tear film stability in healthy Africans. Nigerian Medical

Journal,57(2), 104. doi:10.4103/0300-1652.182071

Cohen, R., Rocque, F. D., Lécuyer, A., Wollner, C., Bodin, M. J., & Wollner, A. (2008). Study

of the acceptability of antibiotic syrups, suspensions, and oral solutions prescribed to

pediatric outpatients. European Journal of Pediatrics,168(7), 851-857. doi:10.1007/s00431-

008-0857-0

Damle, B. D., Kaul, S., Behr, D., & Knupp, C. (2002). Bioequivalence of Two Formulations of

Didanosine, Encapsulated Enteric-Coated Beads and Buffered Tablet, in Healthy Volunteers

and HIV-Infected Subjects. The Journal of Clinical Pharmacology,42(7), 791-797.

doi:10.1177/009127002401102623

Derosa, G., Dangelo, A., Romano, D., & Maffioli, P. (2017). Effects of metformin extended

release compared to immediate release formula on glycemic control and glycemic variability

in patients with type 2 diabetes. Drug Design, Development and Therapy,11, 1481-1488.

doi:10.2147/dddt.s131670

Regimen. (2018, April 10). Retrieved April 20, 2018, from https://www.merriam-

webster.com/dictionary/regimen