ABSTRACT
Aim: In the present study, Sumatriptan succinate was formulated as oral elementary osmotic pump with a zero-order drug release profile. Methodology: The effect of different formulation variables i.e. different types of osmogens, concentrations of osmogen and concentration of coating solution were studied. The in vitro evaluation was carried out in different release media. Result: Highest percentage of drug release was observed at high concentration of mannitol i.e., 1:3 (drug: mannitol). Osmogen with low osmotic pressure (38 atm) showed 71.01% zero-order drug release for 12 hours when compared to that of the osmogen with high osmotic pressure (356 atm) which showed 67.38% of release by zero order. Conclusion: Elementary osmotic pump tablets of Sumatriptan succinate were able to deliver zero-order release up to 12 hours independent of pH of dissolution media and have overcome the problem of chronotherapeutic effect.
ABSTRACT
The present investigation was focused on application of QbD approach to see the effect of formulation variables on buccal mucoadhesive tablets containing anti migraine drug, Sumatriptan succinate to circumvent the first pass effect and to provide sustained release. Risk assessment of critical material and process parameters are linked to critical quality attributes (CQAs) of the product with respect to obtain total quality product profile (TQPP). The effect of critical parameters (polymer: drug ratio, carbopol: HPMC E5 ratio and diluent quantity) were investigated by executing design of experimentation (DoE) using Box-Behnken statistical model. DR10 hr (drug release after 10 hrs), mucoadhesive strength and mucoadhesion time were considered critical quality attributes (CQAs). Sumatriptan succinate buccal mucoadhesive (SBM) tablets were prepared by direct compression method and were evaluated as per pharmacopoeia procedure. Multiple regression analysis and ANOVA were employed to identify and estimate the effect of important parameters and establish their relationship with CQAs and to obtain design space for optimization purpose. The best in-vitro drug release profile, mucoadhesive strength, mucoadhesion time and desired product quality was achieved with the formulation prepared in the region of design space. FDS graph, 3D response graph and Overlay plot were successfully implemented to interpret effects and selection of significant parameters on CQAs. Hence, it can be concluded that formulation parameters affects the SBM tablet and can be successfully optimized using the QbD a novel approach resulting into the SBM tablets which could provide sustained effect and avoid first pass effect.
ABSTRACT
The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs) of an anti-migraine drug, Sumatriptan Succinate (SUM) to enhance convenience and compliance to the elderly and pediatric patients for better therapeutic efficacy. Film former, Hydroxy Propyl Methyl Cellulose along with film modifier/solubilizing agents, Polyvinyl pyrrolidone K30 (PVP K30) and Sodium Lauryl Sulphate (SLS) were used to formulate MDFs. The MDFs were prepared by wet film applicator technique and were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physico-mechanical properties. MDFs with 13% (w/w) of HPMC E5 gave better dissolution properties when compared to HPMC E15. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. Overall, SUM MDFs showed good mechanical properties like tensile strength, folding endurance and % elongation and dissolution properties. These results suggest that the HPMC is an excellent film former which gives rapid drug release.