Abstract

ENHANCEMENT OF DISSOLUTION RATE AND FORMULATION DEVELOPMENT OF VORICONAZOLE TABLETS BY SOLID DISPERSION IN COMBINED CARRIERS

K. P. R. Chowdary*, K. Ravi Shankar and Ch. Chandrasekhar

ABSTRACT

Voriconazole, a widely prescribed antifungal drug belongs to class II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. As such it needs enhancement in the dissolution rate and bioavailability to derive its maximum therapeutic efficacy. The objective of the present study is to prepare and evaluate voriconazole tablets by using solid dispersions in Primojel and Poloxamer 188 prepared as per 22 factorial design. Two methods namely (i) wet granulation and (ii) direct compression methods were used for the preparation of voriconazole tablets employing solid dispersions in combined carriers and a comparative evaluation of the resulting tablets was made. Tablets each containing 50 mg of voriconazole were formulated employing Primojel and Poloxamer 188 as per 22factorial design. For this purpose two levels of Primojel (0 and 1:1 ratio of drug : carrier) and two levels of Poloxamer 188 ( 0 and 5%) were selected and the corresponding four treatments involved in the 22 factorial study were tablets prepared with voriconazole pure drug (F1); tablets prepared with voriconazole- Primojel (1:1) solid dispersion (Fa); tablets prepared with voriconazole – Poloxamer 188 (5%) solid dispersion (Fb) and tablets prepared with voriconazole – Primojel (1:1) – Poloxamer 188 (5%) solid dispersion (Fab). In each case the tablets were prepared by direct compression (DF1, DFa, DFb, and DFab) and by wet granulation methods (WF1, WFa, WFb, WFab) were formulated and evaluated. The disintegration times were in the range 1 min-30 sec to 8min- 20 sec. Tablets prepared by direct compression method disintegrated rapidly when compared to those prepared by wet granulation method. Voriconazole dissolution was very rapid from the tablets formulated employing solid dispersions (Fa, Fb, Fab ) when compared to those formulated using voriconazole pure drug (F1) in both the methods. All the dissolution parameters (PD10, DE30, and K1) indicated rapid dissolution of voriconazole from tablets prepared by direct compression method when compared to those prepared by wet granulation method. In the case of direct compression method the order of increasing dissolution rate (K1) of voriconazole observed with various tablet formulations was DFa > DFb > DFab > DF1. There was no additional increase in the dissolution rate with combined carriers in the case of direct compression method. In the case of wet granulation method the order of increasing dissolution rate (K1) of voriconazole observed with various tablet formulations was WFab > WFa > WFb > WF1. In the case of wet granulation method tablets formulated with combined carriers (WFab) gave significantly higher dissolution rate than is possible with individual carriers alone. Hence solid dispersions in individual carriers, Primojel and Poloxamer 188 in the case of direct compression and solid dispersions in combined carriers of Primojel and Poloxamer188 in the case of wet granulation method are recommended for formulation of voriconazole tablets with fast dissolution characteristics.

Keywords: Voriconazole, Tablets, Direct compression, Wet granulation, Dissolution Rate, Primojel, Poloxamer188, Factorial study.