Development and characterization of an extended release formulation of cyclobenzaprine hydrochloride using lipophilic and hydrophilic matrix components by fusion method

Extended Release (ER) dosage forms are being used widely in the current market which aided in increasing the compliance of patient. But, they are associated with few problems like uncontrolled "Initial Burst Release" [1] (especially in case of freely water soluble drugs) because of the presence of drug on the surface and periphery of matrix tablets, which leads to dose dumping, difficulty in achieving the desired release rate and so on. Using lipophilic matrix forming excipients in combination with hydrophilic components in certain proportions can help in controlling the initial burst release phase and also in achieving the desired release rate of the drug Aim of the present research was to develop and characterize an ER formulation of freely water soluble Cyclobenzaprine hydrochloride (CYC) using different ratios of lipophilic (CompritolRTM 888 ATO) and hydrophilic (KlucelTM Medium grade and MethocelTM K 100M) matrix forming components by fusion method. A 23 full factorial design was employed to screen and optimize the formulation components. Physical mixtures (PM) and ER formulations of different compositions were prepared as per full factorial design and the in-vitro dissolution studies, solid state characterization and rheological studies were performed for them. Solid state characterization was done using different instruments like modulated differential scanning calorimeter (mDSC), powder X-ray diffractometer (PXRD) and Fourier transform infrared spectrophotometer (FTIR). The dissolution profiles of ER formulations showed controlled initial burst release and an extended release profile of 24 hours. Model dependent methods used to determine drug release kinetics disclosed that the dissolution data followed the first order kinetics and the release exponents in Korsmeyer-Peppas equation for all the formulations indicated the Fickian diffusion release except for ER-1 and ER-2, which were assumed to exhibit anomalous release kinetics. Similarity factor (f2) values calculated, demonstrated that the dissolution profiles of ER formulations were significantly different from that of the PM's. Solid state characterization indicated the weak interaction forces between drug and amorphous hydrophilic components, loss of crystallinity in the fusion mixtures and also ensured the chemical integrity of the drug in the formulations. Full factorial design employed in the present study helped in understanding the main (individual) and interaction (combinatorial) effects of lipophilic and hydrophilic excipients on the drug release rate with the help of Minitab RTM17.2.1.;Some interesting aspects like Klucel's behavior that helped in promoting the extended release when in combination with Methocel, though it showed positive impact (as Klucel proportion in the formulation increased, the drug release rate increased) on drug release individually might provide the essence of full factorial design to understand the effects of excipients on the drug release.