Investigating the Targeting Power to Brain Tissues of Intranasal Rasagiline Mesylate-Loaded Transferosomal In Situ Gel for Efficient Treatment of Parkinson's Disease.

Rasagiline mesylate (RSM) is a hydrophilic drug with poor oral bioavailability (36%) because of hepatic first-pass metabolism. The present study focuses on delivering RSM directly to the brain through its inclusion within transferosomal in situ gel administered through the intranasal (IN) route. Transferosomes were formed by the thin-film hydration method with the aid of Design-Expert® software by varying the edge activator (EA) type in the absence or presence of cholesterol. By desirability calculations, the optimum formulation was composed of phosphatidylcholine and sodium deoxycholate as an EA (5:1% w/w) with no cholesterol. The optimum formulation was 198.63 ± 34.98 nm in size and displayed an entrapment efficiency of 95.73 ± 0.09%. Transmission electron microscopy revealed discrete and spherical vesicles. Optimized transferosomes were further incorporated into an in situ gel composed of 0.5% pectin, 15% Pluronic® F-127, and 5% Pluronic® F-68 and tested for the in vivo performance. The systemic as well as brain kinetics were assessed in rats by comparing the IN-administered in situ gel to the IV aqueous solution. The optimum in situ gel showed safety and biocompatibility on rats' nasal mucosa with enhanced brain bioavailability (131.17%). Drug targeting efficiency and direct transport percentage indices (304.53% and 67.16%, respectively) supported successful brain targeting offering direct nose-to-brain drug delivery.

The potential of intranasal delivery of nanocrystals in powder form on the improvement of zaleplon performance: in-vitro, in-vivo assessment.

OBJECTIVE: The present work focuses on improving zaleplon (ZAP) performance through nanosizing its insoluble particles which were then delivered intranasally in powder form. SIGNIFICANCE: Since nanopowders have an exceptional ability to cross cell membrane, their absorption is facilitated in the solid form. Hence, delivering insoluble ZAP nanocrystals (NC) through intranasal route improves its bioavailability due to both nanosization and the escape of hepatic metabolism. METHODS: Nanocrystals were prepared by anti-solvent precipitation followed by probe sonication in presence of Soluplus®, Poloxamer-188 (0.25%), sodium lauryl sulfate (0.5%), and mannitol. Physicochemical evaluation of the prepared NC was done by DSC and XRPD. TGA was performed for stability detection. Ex vivo permeation study through isolated cattle nasal mucosal membrane, in addition to an in vivo bioavailability study was performed for assessment of the prepared NC. RESULTS: Nanosization to 200 nm contributed to the enhancement in dissolution ∼100% within 30 min and reduced half-life to 1.63 min. Confirmation of adsorption of polymers over NC' surface was elucidated. TGA confirmed their thermal stability. Ex vivo permeation study showed a 2.7 enhancement ratio in favor of the prepared NC. Both the extent and rate of NC absorption through nasal mucosa of rabbits were significantly higher (p Ë‚ .05) than in case of oral tablets. The relative bioavailability of NC was increased 3.14 times as compared to the Sleep aid® tablets. CONCLUSION: The intranasal delivery of nanoscale ZAP powder proved to be a successful alternative to oral formulations that suffer poor absorption and limited bioavailability.

A New Crystal Engineering Technique for Dissolution Enhancement of Poorly Soluble Drugs Combining Quasi-emulsion and Crystallo-co Agglomeration Methods.

A target of best dissolution improvement of poorly soluble drugs is a necessity for the success of formulation in industry. The present work describes the preparation, optimization, and evaluation of a new spherical agglomeration technique for glimepiride as a model of poorly soluble drugs. It involved the emulsification of a drug solution containing a dispersed carrier that tailors the crystal habit of the drug to a perfect spherical geometry, in a poor solvent containing a hydrophilic polymer which imparts sphericity and strength to the formed agglomerates. The FTIR peaks of optimized product did not show any sign of chemical interaction between the drug and adsorbed carrier. The DSC and X ray diffractogram showed a peak characteristic of spherical agglomerates with much less intensity than that of glimepiride. The dissolution t1/2 of the drug slightly decreased from 381 min to 334 min in plain agglomerates. Introducing polymers in the aqueous phase of emulsion led to an improvement in the dissolution, reflected in t1/2 ranging from 118 to 231 min. Agglomerates prepared with Starlac/PVP demonstrated the most optimum physicochemical characteristics being spherical, with the best flowability and packability parameters. The t1/2 was as short as 19 min. The new carrier/polymer system offered a synergistic combination that highly contributed in dissolution enhancement of glimepiride. The spheronization and amorphisation offered by the new technique could account for such improvement.