Journal of Pharmaceutical Research

Garg Preeti ¹, Pandey Parijat ¹, Rewri Praveen ², Marwaha Rakesh Kumar ¹, Dureja Harish ¹

Affiliations
1 Department of Pharmaceutical Sciences, M.D.University, Rohtak, 124 001, Haryana, IN
2 Sankara Netharalya, 18 College Road Nungambakkam, Chennai - 600 006, IN

Abstract

The aim of the present work was to prepare acetazolamide (ACZ) loaded nanoparticle-in-microparticle system (NiMS) using ionotropic-gelated chitosan for formulating orally disintegrating tablets (ODTs). The objective behind the study was to investigate the effect of - concentration of drug (X₁), concentration of 1 chitosan (X₂) and volume of sodium tripolyphosphate (NaTPP) (X₃) on the encapsulation efficiency of ACZ from NiMS using Box-Behnken Design. The freeze dried optimized NiMS were further formulated into ODTs using direct compression method. The delivery of ACZ by oral route can be an effective way for the treatment of paediatric glaucoma. The encapsulation efficiency and loading capacity of NiMS-10 was highest at high levels of chitosan concentration and low levels of volume of NaTPP. The encapsulation efficiency and loading capacity of NiMS were lowest at mid levels of volume of NaTPP, which shows that, the proper ratio of chitosan: NaTPP should be present in the formulation for cross linking. A drug entrapment efficiency of about 98.53 ± 3.36% (w/w), loading capacity of 99.62 ± 5.77% (w/w) and particle size of 593 nm were achieved for the optimized batch of nanoparticles. Analysis of Variance (ANOVA) was applied on the encapsulation efficiency of NiMS to study the fitting and the significance of the model. The mathematical model developed in the present study can be further utilized to design NiMS with desired encapsulation efficiency. The batch NiMS-10 showed 96.2% drug release after three hours in phosphate buffer (pH 7.4). Infrared analysis of NiMS-10 showed no interaction between drug and polymer during the formulation process. The particles of NiMS-10 were found spherical in shape. The formulated ODTs have a disintegration time of 35 seconds. The hardness, friability and weight variation of ODTs were found to be within pharmacopoeial limits. In vitro release study revealed that the cumulative percent drug release was found to be 97.8 ± 2.27% in 60 min and the release data followed the first order kinetics. The NiMS approach has been successfully applied for the preparation of ODT of ACZ. The developed ODT can be advantageous for the treatment of glaucoma in paediatric patients.

Keywords

Box-Behnken Design, Chitosan, Acetazolamide, Ionic Gelation Method, Sodium Tripolyphosphate, Orally Disintegrating Tablets.

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