Formulation Development and in Vitro Characterization of Gastroretentive Floating Acyclovir Tablets

Abstract

Background:Acyclovir is the prototype DNA polymerase inhibitor used in management of herpes zoster infections. The bioavailability of the drug is beset by low solubility and low permeability at doses above 400mg. Consequently, high dosages of the drug need to be administered in multiple doses to maintain the therapeutic concentrations required to inhibit viral replication. The high pill burden occasioned leads to suboptimal patient compliance, untoward effects and poor treatment outcomes. The objective of this project was to formulate and characterize gastroretentive floating tablets of acyclovir to increase the mean gastric residence time thereby improving the bioavailability of the drug. A unit dosage of 200mg was selected as it fits into BCS III thus requiring only modification of the drug’s permeability to improve the bioavailability. Methods:A laboratory experimental study design was employed for this study. Preformulation studies were conducted to determine the compatibility of the drug and the excipients using attenuated FTIR spectroscopy. The simplex lattice mixture design was utilized to guide the variation of polymers proportions to investigate the individual contributions of each polymer and their combined effects towards the observed dependent variables. The independent variables were polymers (Hydroxypropyl methyl cellulose K 100M (X1), Hydroxypropyl methyl cellulose K4M (X2) and Carbopol (X3)) whose proportions were varied as per the experimental design. The dependent variables were the floating lag time (Y1), total floating time (Y2), and the cumulative drug released at 3,6, and 8 hours (Y3, Y4, Y5) respectively. The resulting data was keyed into the Design expert software® to generate the polynomials describing the contribution of each independent variable to the outcomes listed above. Validation of the formulation model was done using the optimized formulations for which checkpoint formulation was fabricated and the accuracy of the model established. In addition, the prescribed pharmacopoeial tests for tablets were performed as appropriate. Results and Discussion:Statistical analysis was conducted using the Design expert, STATA and MS Excel as appropriate. All formulations complied with the required pharmacopoeial specifications for weight uniformity, dimensions, friability and assay. Formulation F2 depicted the most desirable profile as all experimental parameters were within the required range for the optimization criterion. F2 depicted 142s, 14h,38.30%,66.02% and 81.20% for floating lag time, total floating time, cumulative drug release at 3,6 and 8 hours respectively. Conclusion:The findings point to the feasibility of fabricating a commercially viable tablet dosage of floating acyclovir that exhibits a controlled drug release profile therefore affording a more convenient dosing schedule.