Study on Effect of Formulation Variables on Drug Release of Bosentan Microspheres

Introduction

A well-known technique to change and delay properties of drug release is the use of microspheres. Microspheres are used to sustain and control drug release when administered orally. Compared to conventional dosages, the administration of drugs using microspheres promotes uniform distribution, leading to consistent absorption and reduced localized discomfort ¹.

Microspheres produce controlled drug delivery, and they provide different structural modifications for altered drug release. Due to their advantages in target specificity and improved patient compliance, microspheres are considered a superior option for drug delivery systems. Conventional formulations have several drawbacks as they require multiple doses Studies show that maintaining a constant plasma concentration through controlled-release dosage forms enhances therapeutic efficacy ². This steady release makes microspheres an attractive solution for prolonged and controlled drug administration.

The drug’s yield, morphology, release, and entrapment within the system are influenced by various factors, including the type of polymer, its concentration, the drug-to-polymer ratio, stirring speed, and concentration of cross-linking agents. Therefore, these elements are essential to the design of microspheres.

The main objective of the study was to evaluate the influence of polymer concentration, drug-to-polymer ratio, stirring speed on particle size, entrapment efficiency (EE), and in vitro release profile of microspheres, with the goal of optimizing the formulation for improved therapeutic efficacy and stability.

Bosentan (BOS), which is used to treat pulmonary arterial hypertension, was selected as a model drug for microsphere preparation due to its poor solubility in aqueous media which necessitates frequent dosing, and increases the cost of therapy ³. Microspheres can enhance the drug’s bioavailability, thereby reducing the frequency of administration, improving patient compliance, and ensuring controlled drug release.

Materialsand Methods

Materials

BOS was a gift sample from SD Fine Chemicals, Mumbai. Sodium alginate (CDH, New Delhi), Calcium chloride (CaCl₂) (Qualigens, Mumbai), Eudragit RL100 (SD Fine Chemicals, Mumbai), Hydroxypropyl methyl cellulose (HPMC K15), Hexane (Spectrochem Pvt. Ltd Mumbai) were commercially procured. All other reagents used in the experiment were of analytical grade and purchased from commercial sources.

Method

Formulation of BOS Microspheres

Twenty-four formulations of BOS microspheres were prepared by the ionotropic gelation process using Sodium alginate, along with two polymers, HPMC K15 and Eudragit RL 100, and CaCl_₂, with twelve formulations at a...