My thesis

In June 2007 I had finished my postgraduate program at School of Pharmacy, Bandung Institute of Technology. Here is the abstract of my thesis:

ABSTRACT

ACYCLOVIR FLOATING TABLET:
FORMULATION AND IN VITRO EVALUATION

MARWATI
NIM: 20705001


Acyclovir is an antiviral agent widely used for the treatment of herpes simplex and varizella zoster. It is soluble only at acidic pH (pKa 2,27) and has a limited absorption in the gastrointestinal tract. Acyclovir is absorbed only in the upper part of the small intestine (duodenum and jejunum). Its elimination half life is about 2.9 hours and its oral bioavailability is low, 20% in average. Due to those behavior the recommended oral dosage of acyclovir immediate release is 200 or 400 mg every 5-6 hours.

The floating gastroretentive drug delivery system can be retained in the stomach and assists in improving delivery of drugs that have a limited absorption in the gastrointestinal regions. This system helps in continuously releasing drugs before it reaches the absorption region, over prolonged time period. Thus it will increase the oral bioavailability and decrease the dosage frequency. The aim of this study was to develop a floating, gastroretentive tablet of acyclovir.

The acyclovir floating tablet was made using wet granulation method. Three kinds of hydroxypropyl methylcellulose (HPMC) K-grade namely K4M, K15M and K100M alone or in combination was used as controlled release and floating agent, while sodium bicarbonate was incorporated as gas-generating agent to minimize the floating lag time.

The floating tablet was evaluated for floating behavior and in vitro dissolution profile. The floating behavior was carried out in 50 ml of 0.1 N hydrochloric acid. The in vitro dissolution was carried according to USP 28 requirement for acyclovir immediate release tablet, for 12 hours.

All formulation tested possessed floating lag time less than one minute and remained
floatable throughout the dissolution studies. The best formulation was chosen based on the highest value of similarity factor (f2) compared to acyclovir zero order release profile and the highest value of cummulative percentage of acyclovir released after 12 hours. The linearity of dissolution profile was also be considered. The best formulation obtained from this research contained 400 mg acyclovir, 60 mg HPMC K4M, 50 mg sodium bicarbonate, 2% w/w talc and 0.5% w/w magnesium stearate in each tablet. This formulation released 85,35 (+/-) 0,62 % of acyclovir in 12 hours, while the floating lag time was less than one minute and the tablet remained floatable throughout the dissolution studies. The release kinetics of acyclovir from the floating system formulated in this study close to the Hixson-Crowel Model.

Keywords: acyclovir, floating tablet, in vitro dissolution