Cyclosporine and Pentoxifylline laden tailored niosomes for the effective management of psoriasis: In-vitro optimization, Ex-vivo and animal study.

Psoriasis is a chronic skin inflammatory auto-immune disorder. Cyclosporine is the drug of choice in severe cases of psoriasis for systemic administration. But its systemic administration leads to some serious side effects like nephrotoxicity and cardiovascular disorders. Pentoxifylline is reported to reduce such side effects of cyclosporine and also it is found useful in the management of psoriasis. In this study, Box-Behnken design was used to prepare and optimize Cyclosporine and Pentoxifylline loaded niosomes. The optimized niosomes were prepared using cholesterol and surfactant (7:3), a total of 500 µmol. Ratio of Tween 80 to span 80 for the preparation of optimized niosome was 0.503 (tween80:span80), and hydration and sonication time were kept at 60 min and 10 min, respectively. Size, Poly Dispersity Index, zeta potential, and % entrapment efficiency of Pentoxifylline and cyclosporine, for optimized niosomes were found to be 179 nm, 0.285, -37.5 mV, 84.6%, and 75.3%, respectively. The optimized niosomes were further studied for in-vitro skin permeation and skin deposition. Though niosomes significantly influenced the permeation of both drugs, only a small amount of drug (both cyclosporine and Pentoxifylline) was permeated through the skin. In comparison with the permeation, the quantity of drug retained in the stratum corneum and viable epidermis (SC and VED) was very high. In the in-vivo studies conducted on mice induced with psoriasis using imiquimod, both the histopathology and psoriasis area severity index has shown marked improvement in the skin condition of mice treated with niosomes loaded with Pentoxifylline and cyclosporine, in comparison with the solution/suspension of individual drugs. The study shows that niosomes could be effectively used for the simultaneous delivery of cyclosporine and Pentoxifylline for the better management of psoriasis.

Development and Characterization of Novel Floating-Mucoadhesive Tablets Bearing Venlafaxine Hydrochloride.

The present investigation is concerned about the development of floating bioadhesive drug delivery system of venlafaxine hydrochloride which after oral administration exhibits a unique combination of floating and bioadhesion to prolong gastric residence time and increase drug bioavailability within the stomach. The floating bioadhesive tablets were prepared by the wet granulation method using different ratios of hydroxypropyl methyl cellulose (HPMC K4MCR) and Carbopol 934PNF as polymers. Sodium bicarbonate (NaHCO3) and citric acid were used as gas (CO2) generating agents. Tablets were characterized for floating properties, in vitro drug release, detachment force, and swelling index. The concentration of hydroxypropyl methyl cellulose and Carbopol 934PNF significantly affects the in vitro drug release, floating properties, detachment force, and swelling properties of the tablets. The optimized formulation showed the floating lag time 72 ± 2.49 seconds and duration of floating 24.50 ± 0.74 hr. The in vitro release studies and floating behavior were studied in simulated gastric fluid (SGF) at pH 1.2. Different drug release kinetics models were also applied. The in vitro drug release from tablets was sufficiently sustained (more than 18 hr) and the Fickian transports of the drug from the tablets were confirmed. The radiological evidence suggests that the tablets remained buoyant and altered position in the stomach of albino rabbit and mean gastric residence time was prolonged (more than > 6 hr).

Development and characterization of novel site specific hollow floating microspheres bearing 5-Fu for stomach targeting.

Multiple-unit-type oral floating hollow microspheres of 5-fluorouracil (5-Fu) were developed using modified solvent evaporation technique to prolong gastric residence time, to target stomach cancer, and to increase drug bioavailability. The prepared microspheres were characterized for micromeritic properties, floating behavior, entrapment efficiency, and scanning electron microscopy (SEM). The in vitro drug release and floating behavior were studied in simulated gastric fluid (SGF) at pH 1.2. The yield of microspheres was obtained up to 84.46 ± 6.47%. Microspheres showed passable flow properties. Based on optical microscopy, particle size was found to be ranging from 158.65 ± 12.02 to 198.67 ± 17.45 µm. SEM confirmed spherical size, perforated smooth surface, and a hollow cavity inside the microspheres. Different kinetic models for drug release were also applied on selected batches.

Formulation and evaluation of novel stomach specific floating microspheres bearing famotidine for treatment of gastric ulcer and their radiographic study

Objective: To develop and characterize multiple-unit-type oral floating microsphere of famotidine to prolong gastric residence time and to target stomach ulcer. Methods: The floating microspheres were prepared by modified solvent evaporation method. Eudragit S-100 was used as polymer. Microspheres were characterized for the micromeritic properties, floating behavior, entrapment efficiency and scanning electron microscopy. The in-vitro release studies and floating behavior were studied in simulated gastric fluid at pH 1.2. Different drug release kinetics models were also applied for all the batches. Selected formulations were also subjected for X-ray radiographic study. Results: Floating microspheres were successfully prepared by modified solvent evaporation technique. Microspheres showed passable flow properties. The maximum yield of microspheres was up to (95.11±0.35)%. On the basis of optical microscopy particle size range was found to be ranging from (52.18±182.00) to (91.64±5.16) μm. Scanning electron microscopy showed their spherical size, perforated smooth surface and a cavity inside microspheres. Microspheres were capable to float up to 20 h in simulated gastric fluid. X-ray radiographic studies also proved its better retention in the stomach. Conclusions:On the basis of the results, such dosage forms may be a good candidate for stomach targeting and may be dispensed in hard gelatin capsules.

Formulation and in-vitro evaluation of floating microballoons of indomethacin.

Objective of present study involves preparation and evaluation of floating microballoons of indometacin as a model drug, to increase its residence time in the stomach without contact with the mucosa. The microballoons were prepared by the emulsion solvent diffusion technique using different ratio of acrylic polymers (Eudragit RS100 and Eudragit S 100) as carriers. The yield of microballoons was up to 91.02 +/- 1.65%. Microballoons showed passable flow properties. On the basis of optical microscopy, particle size range was found to be ranging from 130.90 +/- 12.10 to 170.58 +/- 17.50 microm. Scanning electron microscopy (SEM) confirmed their spherical size, perforated smooth surface and a hollow cavity in them. Microballoons exhibited floating properties for more than 10 h. In vitro drug studies were performed in 0.1 M HCI with 0.1% SLS and phosphate buffer (pH 6.2). Different drug release kinetics models were applied for selected batches.