Pre-formulation investigation and in vitro evaluation of directly compressed ibuprofen-ethocel oral controlled release matrix tablets: A kinetic approach

Abstract

The objective of this study was to develop directly compressed oral controlled-release ibuprofen matrix tablets containing hydrophobic polymer (Ethocel®) of different viscosity gardes (Ethocel®standard 7P, 7FP, 10P, 10FP 100P and 100FP). As ibuprofen like other non-steroidal anti-inflammatory drugs has dosage frequency and severe gastrointestinal tract (GIT) complications and patient non-compliance, so to avoid these problems, controlled release matrices were developed. Before development of matrix tablets, pre-formulation studies were performed for the determination of physicochemical interaction between polymer, drug and co-excipients, using differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) and no interaction was found. Controlled-release matrix tablets were formulated by direct compression method. Effect of partial replacement of lactose by different co-excipients such as HPMC K100M, starch and CMC on the release of drug was also studied. The tablets were subjected to different physicochemical, dimensional and quality controlled tests, such as drug content, weight variations, friability, hardness, thickness and diameter, all these tests were within United Stated Pharmacopoeia (USP) range. The in vitro release profile in phosphate buffer (pH 7.4) for all formulations containing polymer and co-excipients was compared with a formulation developed without polymer and co-excipients for 24 h. Different kinetics models were used, such as first-order equation, zero-order equation, Higuachi equation, Hixon Crowel’s equation and Korsmeyer-Peppas to study and investigate the release mechanism. It was concluded that formulations containing different grades of ethylcellulose polymer showed prolonged release for 6 to 18 h, but the formulation containing polymer Ethocel® standard FP7 premium without co-excipient showed controlled release for 24 h, which can be used to develop controlled release matrices of ibuprofen with optimum release kinetics. All those formulations containing co-excipients showed enhanced release rate. Key words: Ethocel® standard FP premium, Ethocel® standard premium, ibuprofen, matrix tablets, co-excipients, controlled release.