Mangal S. Nagarsenker

Solid lipid nanoparticles have been increasingly utilised for improving oral bioavailability of drugs. Simvastatin is biopharmaceutical class 2 drug with poor oral bioavailability of 5%. In the present study, simvastatin solid lipid nanoparticles were successfully prepared by hot melt emulsification process and optimised with respect to surfactant and lipid concentration, and drug loading. The nanoparticles were characterised for entrapment efficiency, particle size, morphology, crystallinity and thermal behavior. Optimised formulations prepared from solid lipids glyceryl behenate and glyceryl palmitostearate containing Tween 80 as surfactant exhibited satisfactory entrapment efficiencies above 96% and mean particle size below 200 nm. The electron micrographs indicated that lipid nanocarriers were almost spherical in appearance. X-ray diffraction and differential calorimetric studies proved that the drug was amorphised in the lipid matrix and did not crystallise out. To improve the physical as well as chemical stability of formulations, dry adsorbed nanoparticles were prepared by evaporative drying method using a carrier. The adsorbed nanoparticles demonstrated good flow properties and satisfactory reconstitution properties. Pharmacodynamic studies of simvastatin solid lipid nanoparticles revealed improved reduction in total cholesterol values as compared to pure drug powder indicating improved bioavailability.

The aim of study was to develop self-nanoemulsifying pellets (SNEP) for oral delivery of poorly water soluble drug, repaglinide (RPG). Solubility of RPG in oily phases and surfactants was determined to identify components of self-nanoemulsifying drug delivery system (SNEDDS). The surfactants and cosurfactants were screened for their ability to emulsify oily phase. Ternary phase diagrams were constructed to identify nanoemulsification area for the selected systems. SNEDDS formulations with globule size less than 100 nm were evaluated for in vivo anti-hyperglycemic activity in neonatal streptozotocin rat model. A significant reduction in glucose levels was produced by optimized SNEDDS formulation in comparison to the control group. The optimized SNEDDS formulations were pelletized via extrusion/spheronization technique using microcrystalline cellulose and lactose. SNEP were characterized by X-ray powder diffraction and scanning electron microscopy. X-ray diffraction study indicated loss of crystallinity of RPG in SNEP. The SNEP exhibited good flow properties, mechanical strength and formed nanoemulsion with globule size less than 200 nm. SNEP showed in vitro release of more than 80% RPG in 10 min which was significantly higher than RPG containing reference pellets. In conclusion, our studies illustrated that RPG, a poorly water soluble drug can be successfully formulated into SNEP which can serve as a promising system for the delivery of poorly water soluble drugs.

A preconcentrate containing Carbamazepine (CBZ) was designed, with the objective to improve its oral bioavailability, which on dilution with aqueous vehicles in vitro/in vivo would yield CBZ nanosuspension in situ. When preconcentrate containing hydrophilic stabilizer alone was diluted with aqueous medium, CBZ precipitated as needle shaped crystals within few minutes, due to Ostwald ripening and probably, due to conversion to dihydrate polymorph. Combination of lipophilic stabilizers and hydrophilic stabilizers imparted adequate colloidal stability to CBZ nanosuspension. Preconcentrate containing a mix of different stabilizers which could yield nanosuspension in situ was optimized with respect to colloidal stability and mean particle size. Preconcentrate containing Tween 80 (31.4% w/v) as hydrophilic stabilizer and Labrafil M1944 CS (20.9 %w/v) as lipophilic stabilizer yielded mean particle size and polydispersity index of 192.7± 5.65 nm and 0.35± 0.02, respectively, on dilution with aqueous medium in situ. This optimized formula of nanoprecipitating preconcentrate (NPP) yielded CBZ nanosuspension in situ on dilution with aqueous media. The size of CBZ NPP dispersed in water was confirmed with TEM studies, which also provided information on surface morphology of CBZ nanosuspension. The CBZ NPP preconcentrate was converted to free flowing granules (NPPG 1) by adsorption on to Aerosil R 974, for ease of handling. Amorphous state of CBZ in NPPG 1 system as indicated by XRD studies coupled with greater surface area of nanosized CBZ particles could have resulted in improved dissolution velocity of CBZ as compared to CBZ suspension, as observed during in vitro dissolution testing. Anti-epileptic studies in mice demonstrated CBZ NPP superior to plain CBZ suspension in delaying onset of seizures and in reducing mortality.

The objective of the present investigation was to establish potential of commercially available soy polysaccharide (Emcosoy®) for colon drug delivery. The soy polysaccharide–ethyl cellulose films...

Solid lipid nanoparticles (SLNs) of duloxetine hydrochloride (DLX) were prepared to circumvent the problems of DLX, which include acid labile nature, high first-pass metabolism, and high-dosing...

The objective of the present investigation was to study the ability of sulfobutyl ether₇-β-cyclodextrin to form an inclusion complex with carbamazepine, an anti-epileptic drug with poor water solubility. The formation of the complex was carried out using the industrially feasible spray-drying method. The inclusion complex and physical mixtures were characterized by various techniques such as differential scanning calorimetry (DSC), infrared (IR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and molecular modeling. The DSC, IR, and NMR studies confirmed the formation of an inclusion complex between carbamazepine and sulfobutyl ether₇ β-cyclodextrin whereas XRD studies indicated an amorphous nature of the inclusion complex. Molecular modeling studies disclosed different modes of interaction between carbamazepine and sulfobutyl ether₇ β-cyclodextrin with good correlation with experimental observations. The inclusion complex exhibited significantly higher in vitro dissolution profile as compared with pure carbamazepine powder. The in vivo anti-epileptic activity of carbamazepine/sulfobutyl ether₇ β-cyclodextrin complex was evaluated in pentylenetetrazole-induced convulsions model. The carbamazepine/sulfobutyl ether₇ β-cyclodextrin complex showed significantly higher anti-epileptic activity (p <0.01) as compared with that of carbamazepine suspension on oral administration.

The objective of the present study was to synthesize monomethoxypolyethyleneglycol-5000 cholesteryl ester [PEG–CH] as a cost-effective substitute for polyethyleneglycol–phosphatidylethanolamine and to evaluate the influence of its incorporation in liposomal bilayers for surface modification. PEG–CH was synthesized and characterized by infrared (IR), proton nuclear magnetic resonance spectroscopy (¹H NMR), and differential scanning calorimetry (DSC) studies. Influence of incorporation of PEG–CH in liposomes was evaluated on various parameters such as zeta potential, DSC, and encapsulation efficiency of a hydrophilic drug pentoxyfylline. Conventional and PEG–CH containing pentoxyfylline liposomes were formulated and their stability was evaluated at 4°C for 3 months. PEG–CH could be successfully synthesized with good yields and the structure was confirmed by IR, DSC, and ¹H NMR. The incorporation of PEG–CH in liposomes resulted in reduction of the zeta potential and broadening of the DSC endotherm. Furthermore, incorporation of PEG–CH in liposomes decreased the encapsulation efficiency of pentoxifylline in liposomes when compared to conventional liposomes. Conventional and PEG–CH containing pentoxyfylline liposomes did not show any signs of pentoxyfylline degradation when stored at 4°C for 3 months.

Present study describes microencapsulation of eugenol using gelatin-sodium alginate complex coacervation. The effects of core to coat ratio and drying method on properties of the eugenol microcapsules were investigated. The eugenol microcapsules were evaluated for surface characteristics, micromeritic properties, oil loading and encapsulation efficiency. Eugenol microcapsules possessed good flow properties, thus improved handling. The scanning electron photomicrographs showed globular surface of microcapsules prepared with core: coat ratio1:1.The treatment with dehydrating agent isopropanol lead to shrinking of microcapsule wall with cracks on it. The percent oil loading and encapsulation efficiency increased with increase in core: coat ratio whereas treatment with dehydrating agent resulted in reduction in loading and percent encapsulation efficiency of eugenol microcapsules.

The objective of the present investigation was to formulate solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for improving the dermal delivery of a local anesthetic agent...