FORMULATION AND In-vitro EVALUATION OF CONTROLLED RELEASE TRAMADOL HYDROCHLORIDE MICROSPHERES AND STUDY OF THE FACTORS AFFECTING DRUG ENTRAPMENT EFFICIENCY AND DRUG RELEASE USING CENTRAL COMPOSITE DESIGN

Background: Microspheres are frequently used as polymeric controlled drug delivery devices so that predetermined and specific drug release is obtained. Wastage of drug during formulation, low drug entrapment efficiency, burst release and inefficiency in designing a controlled release formulation are the major drawbacks of such micro particulate system. This research entails the study of different formulation variables and design of an improved microspherical system which properly addresses the problems inherent in manufacture of microspheres with solvent evaporation technique.

Methods: In this experiment, 20 formulations of Tramadol Hydrochloride microspheres were formulated with the Central Composite Design with MINITAB ver.16.1 taking Tramadol hydrochloride as drug and HPMC K100 M as a polymer in different ratios with solvent evaporation method after performing the drug-excipient compatibility and preformulation studies of flow properties. Different relations between the process variables and results were observed and described. The result obtained from the design was used for the formulation of an optimized batch with the help of response optimizer (Minitab Ver 16.1) with improved entrapment efficiency and controlled release dissolution profile over fourteen hours.

Results: The optimized formulation showed that when formulation variables such as polymer percentage, tween 80, stirring speed are maintained in order 73%, 0.46% and 1603 rpm respectively, a zero order controlled release profile for 14 hours with a release of 18.96%, 50.25% and 88.40% of the drug during 1,6 and 14 hours and maximum entrapment efficiency (73%) can be obtained.

Conclusion: The experiment proves that experimental setup with high concentration of polymer, low surfactant and a high stirring speed can be used to design a controlled release formulation with maximum entrapment efficiency.