Screening of Most Effective Variables for Development of Gastroretentive Mucoadhesive Nanoparticles by Taguchi Design

Ankit Anand Kharia,Akhlesh Kumar Singhai

doi:10.1155/2013/348095

Ankit Anand Kharia, Akhlesh Kumar Singhai

Open Access

https://doi.org/10.1155/2013/348095

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Abstract

The objective of this study was the selection of the most influential variable for the preparation of gastroretentive mucoadhesive nanoparticles of acyclovir. Nanoparticles were prepared by one-step desolvation method; effect of formulation and processing variables on various response variables were studied by a Taguchi standard orthogonal array L8 design. Independent variables studied were the amount of gelatin, amount of glutaraldehyde, amount of Pluronic F-68, acetone addition rate, pH, stirring time, and stirring speed. The dependent variables studied were the particle size, polydispersity index, amount of drug released in 6 h, time required to release 60% of drug, entrapment efficiency, loading efficiency, and mucoadhesiveness. The size of all nanoparticulate formulations prepared as per the experimental design (Taguchi screening design) varied between 165 and 1610 nm, PDI between 0.360 and 1.00, bioadhesiveness between 3.959 and 11.02 g, cumulative percent drug release in 24 h between 40.74 and 72.48, entrapment efficiency between 15.70 and 83.12, and loading efficiency between 39.72 and 80.49. Pareto ranking analyses showed that the two most important factors affecting the selected responses were amount of gelatin and amount of Pluronic F-68 (P<0.05).

Highlights

Acyclovir is a cyclic analogue of the natural nucleoside 2deoxyguanosine, clinically used in the treatment of Herpes simplex, Varicella zoster, Cytomegalovirus, and Epstein barr virus infections [1]
Gelatin and Pluronic F-68 were purchased from HiMedia Laboratories Pvt., Ltd., Mumbai, India
Polydispersity index (PDI), amount of drug released in 6 h (Q6), time required to release 60% of drug (T60%), entrapment efficiency, loading efficiency, and mucoadhesiveness were the key response variables investigated thoroughly for selecting the significant formulation and response factors

Summary

Introduction

Acyclovir is a cyclic analogue of the natural nucleoside 2deoxyguanosine, clinically used in the treatment of Herpes simplex, Varicella zoster, Cytomegalovirus, and Epstein barr virus infections [1]. Several attempts are being made to increase the gastric retention of drugs, like intragastric floating systems, hydrodynamically balanced systems, extendable or expandable, microporous compartment system, microballoons, bio/mucoadhesive systems, high-density systems, and superporous biodegradable hydro gel systems [7] After oral administration, such a dosage form would be retained in the stomach for several hours and would release the drug there in a controlled and prolonged manner, so that the drug could be supplied continuously to its absorption sites in the upper gastrointestinal tract [8]. Taguchi methods or an orthogonal array have been widely used to optimize the reaction variables by formulating a minimum number of experiments This approach helps to identify the influence of individual factors and establish the relationship between variables and operational conditions [13]. These mucoadhesive polymeric nanoparticles in the stomach will offer diverse advantages such as (a) longer residence time of the dosage form on gastric mucosa which will improve absorption of the drug and increase the bioavailability, (b) higher drug concentration at the site of adhesion absorption, which will create a driving force for the paracellular passive uptake, and (c) immediate absorption from the bioadhesive drug delivery system without previous dilution and probable degradation in the luminal fluids [16]

Materials and Methods

Evaluation of Formulations

Results and Discussion

Conclusion