Design, Development and Delivery of Rasagiline Mesylate from Monolithic Drug in Adhesive Matrix Patches

The purpose of this research was to prepare and evaluate monolithic drug-in-adhesive type patches of Rasagiline Mesylate (RM) containing penetration enhancer and having seven day wear property. Preformulation studies like solubility in permeation enhancers, compatibility study, transmission study, uptake study and crystallization study of Rasagiline Mesylate in various pressure sensitive adhesive polymers were performed. Transdermal system was prepared by solvent casting method. The effects of various permeation enhancers (Propylene Glycol, Oleic Acid, Isopropyl Palmitate, and lauryl lactate) on the ex-vivo transcutaneous absorption of Rasagiline Mesylate through human cadaver skin were evaluated by modified Franz diffusion cell system. Ex-vivo transcutaneous absorption of prepared transdermal patch was performed using different concentration of Lauryl lactate (3%, 5%, and 7%). In-vitro Adhesion testing (Peel, tack shear etc.) was performed on different dry GSM (Grams per Square Meter) of patch like 80GSM, 100 GSM and 150 GSM. The final transdermal patches were tested for appearance, weight of matrix, thickness, % assay of drug content, in-vitro adhesion testing, cold flow study and ex-vivo skin permeation studies. Based on crystallization study and adhesion testing, Durotak-4098 (14% drug concentration) was selected as pressure sensitive adhesive. Patch containing Lauryl lactate showed highest cumulative permeation compared to other permeation enhancers. The patch containing 5% laurel lactate showed greater transdermal flux (2.36 µg/cm2 /hr). Patch with 150 dry GSM showing promising adhesion properties. Backing film Scotchpak 9723 and release liner Saint Gobain 8310 was selected based on transmission and uptake study of Rasagiline Mesylate. Stability study indicates that developed formulation remains stable. In conclusion, the present research confirms the practicability of developing Rasagiline Mesylate transdermal system.

Development and Ex vivo evaluation of Rasagiline Mesylate mucoadhesive microemulsion for intranasal delivery using Box-Behnken design

Rasagiline mesylate (RM), an irreversible, selective inhibitor of MAO-B enzyme, is used in the treatment of Parkinson’s disease as oral tablets. It has low oral bioavailability (36%) due to hepatic first pass metabolism. Oral route of administration is associated with nausea and vomiting. Hence present research work was aimed to develop intranasal RM- loaded mucoadhesive microemulsions for brain targeting via olfactory pathway. The microemulsions were developed using Box Behnken design and evaluated for globule size, PDI, Zeta potential, pH, viscosity and ex vivo permeation on excised porcine nasal mucosa. Based on drug solubility, Capmul MCM, Tween 20 and Transcutol P were selected as oil, surfactant and cosurfactant respectively. Microemulsions were prepared by water titration method. Pseudoternary phase diagrams were constructed and the levels of surfactants, oil were selected. The influence of independent variables such as oil, Smix and water on responses size, zeta potential and flux were studied with the help of polynomial equations, contour plots and 3D response surface plots generated by design expert software. Optimized microemulsion formulation (ME18) was composed of oil (Capmul MCM), Smix (Tween 20: Transcutol P; 1:1), water and drug in the ratio 5:42:65:5.The globule size, zeta potential and flux of the optimized microemulsion was 150 nm, -29.6 mV and 291.7 μg/cm2/h respectively. Mucoadhesive agent (Chitosan) was added at 0.5% concentration to optimized microemulsion formulation (MME18). The size, zeta potential and flux of the MME18 was 176.4 nm, 12.1 mV and 323.1 μg/cm2/h respectively. The flux of ME18 and MME 18 was significantly higher than drug solution. The enhancement ratio of MME 18 was 4.2 times to that of drug solution, indicating potential advantage of microemulsion formulation.