Hetal Thakkar

Albumin microspheres as carriers for the antiarthritic drug celecoxib

The present study investigates the preparation of celecoxib-loaded albumin microspheres and the biodistribution of technetium-99m (99mTc)-labeled celecoxib as well as its microspheres after intravenous administration. Microspheres were prepared using a natural polymer BSA using emulsification chemical cross-linking method. The prepared microspheres were characterized for entrapment efficiency, particle size, and in vitro drug release. Surface morphology was studied by scanning electron microscopy. Biodistribution studies were performed by radiolabeling celecoxib (CS) and its microspheres (CMS) using99mTc and injecting arthritic rats intravenously. The geometric mean diameter of the microspheres was found to be 5.46 μm. In vitro release studies indicated that the microspheres sustained the release of the drug for }6 days. Radioactivity measured in different organs after intravenous administration of celecoxib solution showed a significant amount of radioactivity in the liver and spleen. In case of celecoxib-loaded microspheres, a significant amount of radioactivity accumulated in the lungs. No significant difference (P>.1) in the radioactivity was observed between the inflamed joint and the noninflamed joint following intravenous injection of99mTc-CS. However, in case of the microspheres (CMS), the radioactivity present in the inflamed joint was 2.5-fold higher than in the noninflamed joint. The blood kinetic studies revealed that celecoxib-loaded albumin microspheres exhibited prolonged circulation than the celecoxib solution.

Formulation and characterization of lipid-based drug delivery system of raloxifene-microemulsion and self-microemulsifying drug delivery system

Background: Raloxifene, a second-generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. Materials and Methods: In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS) formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM) and in vitro intestinal permeability. Results: The results indicated that high drug loading, optimum size and desired zeta potential and transparency could be achieved with both SMEDDS and microemulsion. The TEM studies indicated the absence of aggregation with both the systems. The in vitro intestinal permeability results showed that the permeation of the drug from the microemulsion and SMEDDs was significantly higher than that obtained from the drug dispersion and marketed formulation. Conclusion: Lipid based formulations such as microemulsion and Self Microemulsifying drug delivery systems are expected to increase the oral bioavailability as evidenced by the increased intestinal permeation.

Efficacy of chitosan microspheres for controlled intra-articular delivery of celecoxib in inflamed joints.

The use of polymeric carriers in formulations of therapeutic drug delivery systems has gained widespread application, due to their advantage of being biodegradable and biocompatible. In this study, we aimed to prepare celecoxib‐loaded chitosan microspheres for intra‐articular administration and to compare the retention of the celecoxib solution and chitosan microspheres in the joint cavity. The microspheres were characterized for entrapment efficiency, particle size and surface morphology by scanning electron microscopy. In‐vitro drug release studies of microspheres revealed that the microspheres are able to control the release of celecoxib over a period of 96 h. Biodistribution studies of celecoxib and chitosan microspheres were performed by radiolabelling with 99mTc and injecting intra‐articularly in rats. The study indicated that following intra‐articular administration the distribution of the drug to the organs, like liver and spleen, is very rapid compared with that of the microspheres. Compared with the drug solution, a 10‐fold increase in the concentration of the drug in the joint was observed 24 h post intra‐articular injection (P < 0.005) when drug was encapsulated in microspheres.

Celecoxib incorporated chitosan microspheres: in vitro and in vivo evaluation.

Recently, considerable interest has been focussed on the use of biodegradable polymers for specialized applications such as controlled release of drug formulations; meanwhile, microsphere drug delivery systems using various kinds of biodegradable polymers have been studied extensively during the past two decades. In the present investigation, it was aimed to prepare microsphere formulations of celecoxib using a natural polymer, chitosan as a carrier for intra-articular administration to extend the retention of the drug in the knee joint. Microsphere formulations were evaluated in vitro for particle size, entrapment efficiency, surface morphology and in vitro drug release. For in vivo studies, 99mTechnetium- labeled glutathione was used as a radiopharmaceutical to demonstrate arthritic lesions by gamma scintigraphy. Evaluation of arthritic lesions post therapy in rats showed a significant difference (P<0.05) in the group treated with celecoxib solution compared to the group treated with celecoxib loaded chitosan microspheres.

Development and characterization of nanosuspensions of olmesartan medoxomil for bioavailability enhancement

Background: Olmesartan medoxomil (OLM), an anti-hypertensive agent administered orally has absolute bioavailability of only 26% due to the poor aqueous solubility (<7.75 μg/ml). The present investigation aimed at enhancing the oral bioavailability of OLM by improving its solubility and dissolution rate by preparing nanosuspensions. Materials and methods: The nanosuspensions of OLM were prepared using media milling technique followed by its lyophilization using mannitol as a cryoprotectant. Various formulation as well as process parameters were optimized in order to achieve desirable size and saturation solubility. Characterization of the prepared nanosuspension was done with respect to particle size, zeta potential, saturation solubility, dissolution rate, morphology study (TEM), in-vitro and exvivo drug diffusion study. Evaluation of the crystalline state before and after particle size reduction was done by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Results: The results indicated that the initial crystalline state is preserved following particle size reduction and that the saturation solubility, dissolution velocity and diffusion rate of the drug from the nanosuspension is significantly higher than that of the plain drug suspension as well as from the marketed tablet formulation. Conclusion: Nanosuspension seems to be a promising approach for bioavailability enhancement because of the simple method of its preparation and its universal applicability.

Formulation and evaluation of Itraconazole nanoemulsion for enhanced oral bioavailability.

Abstract Itraconazole (ITR), an antifungal agent has poor bioavailability due to low aqueous solubility. The present investigation aimed at development of ITR nanoemulsion to enhance its oral bioavailability. ITR nanoemulsion was prepared using Capmul MCM C8 as oil, Pluronic F68 as co-surfactant and Cremophore EL as surfactant using high speed stirring, followed by probe sonication. Nanoemulsion with average globule size of 100.9 nm and zeta potential of −35.9 ± 1.2 mV was able to penetrate well into the intestinal membrane as confirmed by the laser confocal scanning microscopy and ex vivo intestinal permeability study. Antimycotic study confirmed the efficacy of ITR nanoemulsion. Significantly higher values of pharmacokinetic parameters the formulation than the plain drug and marketed formulation indicated an increase in the bioavailability of ITR. The prepared nanoemulsion was stable at both, refrigerated and room temperature conditions. Nanoemulsion of ITR seems to be a promising formulation for enhancement of its oral bioavailability.

Statistically optimized fast dissolving microneedle transdermal patch of meloxicam: A patient friendly approach to manage arthritis

Introduction The long term administration of Meloxicam for the management of arthritis, a chronic disorder, results in gastrointestinal disturbances leading to poor patient compliance. Considering the favorable molecular weight, therapeutic dose, biological half‐life and log P value of meloxicam for transdermal delivery, its fast dissolving microneedle patch, with an ability to breach the stratum corneum and efficiently deliver the cargo to deeper skin layers, were developed. Methods Microneedle patch of low molecular weight polyvinyl alcohol and polyvinylpyrrolidone was prepared using Polydimethylsiloxane micromolds. The ratio of polyvinyl alcohol to polyvinyl pyrrolidone and solid content of matrix solution was optimized to achieve maximum needle strength. The optimized batch was extensively evaluated for in vitro dissolution, drug release, stability, ex vivo skin permeation/deposition, histopathology and in vivo pharmacodynamic study. Results The patch containing 9:1 polyvinyl alcohol to polyvinylpyrrolidone ratio with 50% solid content had shown maximum axial needle fracture force (0.9 N) suitable for penetrating the skin. The optimized batch was found to be fast dissolving and released almost 100% drug in 60 min following dissolution controlled kinetics. The formulation showed a significant drug deposition within skin (63.37%) and an improved transdermal flux (1.60 &mgr;g/cm2/h) with a 2.58 fold enhancement in permeation as compared to plain drug solution. The formulation showed a comparable anti‐inflammatory activity in rats when compared to its existing approved marketed oral tablet. Histopathology and stability evaluations demonstrated acceptable safety and shelf‐life of the developed formulation. Conclusion The successful verification of safety, efficacy and stability of microneedle patch advocated the suitability of the formulation for transdermal use. &NA; Graphical abstract Figure. No Caption available.

Vincristine-sulphate-loaded liposome-templated calcium phosphate nanoshell as potential tumor-targeting delivery system.

Vincristine-sulfate–loaded liposomes were prepared with an aim to improve stability, reduce drug leakage during systemic circulation, and increase intracellular uptake. Liposomes were prepared by the thin-film hydration method, followed by coating with calcium phosphate, using the sequential addition approach. Prepared formulations were characterized for size, zeta potential, drug-entrapment efficiency, morphology by transmission electron microscopy (TEM), in vitro drug-release profile, and in vitro cell cytotoxicity study. Effect of formulation variables, such as drug:lipid ratio as well as nature and volume of hydration media, were found to affect drug entrapment, and the concentration of calcium chloride in coating was found to affect size and coating efficiency. Size, zeta potential, and TEM images confirmed that the liposomes were effectively coated with calcium phosphate. The calcium phosphate nanoshell exhibited pH-dependent drug release, showing significantly lower release at pH 7.4, compared to the release at pH 4.5, which is the pH of the tumor interstitium. The in vitro cytotoxicity study done on the lung cancer cell line indicated that coated liposomes are more cytotoxic than plain liposomes and drug solution, indicating their potential for intracellular drug delivery. The cell-uptake study done on the lung cancer cell line indicated that calcium-phosphate–coated liposomes show higher cell uptake than uncoated liposomes.

Gemcitabine hydrochloride-loaded functionalised carbon nanotubes as potential carriers for tumour targeting

The objective of the present work was to formulate gemcitabine hydrochloride loaded functionalised carbon nanotubes to achieve tumour targeted drug release and thereby reducing gemcitabine hydrochloride toxicity. Multiwalled carbon nanotubes were functionalised using 1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000. Optimised ratio 1:2 of carbon nanotubes:1,2-distearoylphosphatidyl ethanolamine-methyl polyethylene glycol conjugate 2000 was taken for loading of gemcitabine hydrochloride. The formulation was evaluated for different parameters. The results showed that maximum drug loading efficiency achieved was 41.59% with an average particle size of 188.7 nm and zeta potential of −10−1 mV. Scanning electron microscopy and transmission electron microscopy images confirmed the tubular structure of the formulation. The carbon nanotubes were able to release gemcitabine hydrochloride faster in acidic pH than at neutral pH indicating its potential for tumour targeting. Gemcitabine hydrochloride release from carbon nanotubes was found to follow Korsmeyer-Peppas kinetic model with non-Fickian diffusion pattern. Cytotoxic activity of formulation on A549 cells was found to be higher in comparison to free gemcitabine hydrochloride. Stability studies indicated that lyophilised samples of the formulation were more stable for 3 months under refrigerated condition than at room temperature. Thus carbon nanotubes can be promising carrier for the anticancer drug gemcitabine hydrochloride.

Physiologically activated phase transition systems for improved ocular retention of ketorolac tromethamine.

In present investigation, novel physiologically activated phase transition systems for Ketorolac Tromethamine was developed. In-situ gelling systems: pH sensitive gel using carbopol 980 and HPMC K100LV, ion sensitive gel using gallan gum and temperature sensitive gel using Poloxamer 407 and Poloxamer 188 were developed. The drug content, content uniformity, pH, optical transmittance, rheological property, bioadhesive strength, in-vitro drug release, ocular irritation and stability study were evaluated. Characterization revealed that gels were conforming to all criteria required for ocular delivery in terms of stability on sterilization, long residence time, non-irritability and sustained drug release without affecting vision. Thus, In-situ gels can be a promising alternative to the prevalent market formulations.