Spray-dried alginate microparticles for potential intranasal delivery of ropinirole hydrochloride: development, characterization and histopathological evaluation.

Ropinirole hydrochloride (RH) is an anti-Parkinson drug with relativity low oral bioavailability owing to its extensive hepatic first pass metabolism. Spray-dried mucoadhesive alginate microspheres of RH were developed and characterized followed by histopathological evaluation using nasal tissue isolated from sheep. Spherical microparticles having high product yield (around 70%) were obtained when the inlet temperature of spray drying was 140 °C. Fourier Transform Infrared (FTIR) studies revealed the compatibility of the drug with the polymer, and scanning electron microscopy (SEM) showed that drug-loaded microparticles were spherical, and the apparent surface roughness was inversely related to the ratio of polymer to drug. Furthermore, size of the spray-dried particles were in the range of 2.5-4.37 µm, depending on formulation. All formulations had high drug encapsulation efficiencies (101-106%). Drug loaded into the polymeric particles was in the amorphous state and drug molecules were molecularly dispersed in the polymeric matrix of the microparticles which were revealed by X-ray diffraction and differential scanning calorimetry (DSC), respectively. The in vitro drug release was influenced by polymer concentration. Histopathological study demonstrated that RH-loaded sodium alginate microparticles was safe to nasal epithelium. In conclusion, spray drying of RH using sodium alginate polymer has produced microparticles of suitable characteristics for potential intranasal administration.

Proliposome tablets manufactured using a slurry-driven lipid-enriched powders: Development, characterization and stability evaluation.

Proliposome powders were prepared via a slurry method using sorbitol or D-mannitol as carbohydrate carriers in 1:10 or 1:15 w/w lipid phase to carrier ratios. Soya phosphatidylcholine (SPC) and cholesterol were employed as a lipid phase and Beclometasone dipropionate (BDP) was incorporated as a model drug. Direct compaction using a Minipress was applied on the lipid-enriched powder in order to manufacture proliposome tablets. Sorbitol-based proliposome tablets in a 1:15 w/w ratio were found to be the best formulation as it exhibited excellent powder flowability with an angle of repose of 25.62 ±â€¯1.08°, and when compacted the resultant tablets had low friability (0.20 ±â€¯0.03%), appropriate hardness (crushing strength) (120.67 ±â€¯12.04 N), short disintegration time (5.85 ±â€¯0.66 min), and appropriate weight uniformity. Moreover, upon hydration into liposomes, the entrapment efficiency for sorbitol formulations in both 1:10 and 1:15 lipid to carrier ratios were significantly higher (53.82 ±â€¯6.42% and 57.43 ±â€¯9.12%) than D-mannitol formulations (39.90 ±â€¯4.30% and 35.22 ±â€¯6.50%), respectively. Extended stability testing was conducted for 18 months, at three different temperature conditions (Fridge Temperature (FT; 6 °C), Room Temperature (RT; 22 °C) and High Temperature (HT; 40 °C)) for sorbitol-based proliposome tablets (1:15 w/w ratio). Volume median diameter (VMD) and zeta potential significantly changed from 5.90 ±â€¯0.70 µm to 14.79 ±â€¯0.79 µm and from -3.08 ±â€¯0.26 mV to -11.97 ±â€¯0.26 mV respectively at month 18, when samples were stored under HT conditions. Moreover, the entrapment efficiency of BDP decreased from 57.43 ±â€¯9.12% to 17.93 ±â€¯5.37% following 18 months storage under HT conditions. Overall, in this study for the first time, proliposome tablets were manufactured and thoroughly characterized, and sorbitol showed to be a promising carrier.

Ethanol-based proliposome delivery systems of paclitaxel for in vitro application against brain cancer cells.

In this study the anticancer activity of paclitaxel-loaded nano-liposomes on glioma cell lines was investigated. Soya phosphatidylcholine:cholesterol (SPC:Chol), hydrogenated soya phosphatidylcholine:cholesterol (HSPC:Chol) or dipalmitoylphosphatidylcholine:cholesterol (DPPC:Chol) in 1:1 mole ratio were used to prepare ethanol-based proliposomes. Following hydration of proliposomes, the size of resulting vesicles was subsequently reduced to nanometer scale via probe-sonication. The resulting formulations were characterized in terms of size, zeta potential and morphology of the vesicles, and entrapment efficiency of paclitaxel (PX) as well as the final pH of the preparations. DPPC-liposomes entrapped 35-92% of PX compared to 27-74% and 25-60% entrapped by liposomes made from SPC and HSPC formulations respectively, depending on drug concentration. The entrapment efficiency of liposomes was dependent on the lipid bilayer properties and ability of PX to modify surface charge of the vesicles. In vitro cytotoxicity studies revealed that PX-liposome formulations were more selective at inhibiting the malignant cells. The cytotoxicity of PX-liposomes was dependent on their drug-entrapment efficiency. This study has shown PX-liposomes generated from proliposomes have selective activity against glioma cell lines, and the synthetic DPPC phospholipid was most suitable for maximized drug entrapment and highest activity against the malignant cells in vitro.