ENHANCED ORAL BIOAVAILABILITY OF TENOFOVIR FROM IONOTROPICALLY GELLED MICROBEADS

Objective: The main objective of the present investigation was to develop microbeads of tenofovir. Tenofovir, a BCS class III drug has a poor bioavailability of 25%, and it is administered 300 mg once a day. By incorporating the drug into a microparticulate carrier, it is expected that the dissolution profile and the oral bioavailability may be increased. Methods: Reinforced gellan-chitosan and calcium chloride beads of tenofovir were prepared by ionotropic gelation method employing various different concentrations of gellan, chitosan, calcium chloride and tenofovir. The beads were evaluated for various physico-chemical parameters such as particle size determination, drug entrapment efficiency, swelling studies, infra red spectroscopy study, differential scanning calorimetry, x-ray diffraction analysis, scanning electron microscopy, in vitro drug release study, cytotoxicity study and in vivo oral bioavailability studies. Results: From the results, it can be concluded that the formulation TB-III exhibited higher drug entrapment efficiency (46.09±0.21), a higher swelling index, sustained drug release for a period of 24 h. The pharmacokinetic profile of the drug from microbeads exhibited an increased oral bioavailability (1.25 times higher than that of pure drug), decreased elimination rate (1.32 times lesser for drug in microbeads) with prolonged elimination half-life (1.32 times higher than pure tenofovir). Conclusion: Tenofovir loaded microbeads demonstrated as a better delivery system for the modified release of drug and also to navigate the drawbacks associated with the conventional therapy

FORMULATION AND CHARACTERISATION OF SUSTAINED RELEASE MICROBEADS LOADED WITH ZALTOPROFEN

Objective: The main aim of the present investigation was to formulate and evaluate microbeads of zaltoprofen. Zaltoprofen, a BCS class II drug used in the treatment of rheumatoid arthritis. Zaltoprofen has a shorter half-life of 2.8 h, and it is administered at a dose of 80 mg thrice a day. By encapsulating the drug into microbeads, it is expected that the release of the drug would be prolonged and thereby, it reduces the frequency of administration and better patient compliance may be improved. Methods: Gellan-chitosan and calcium chloride beads of zaltoprofen were prepared employing ionotropic gelation method using different concentrations of gellan, chitosan, calcium chloride and zaltoprofen. The microbeads were evaluated for its various Physico-chemical parameters such as particle size determination, drug entrapment efficiency, infrared spectroscopy study, differential scanning calorimetry, X-ray diffraction analysis, scanning electron microscopy, in vitro drug release study and in vivo oral bioavailability studies. Results: The results suggested that the batch FG-II exhibited higher drug entrapment efficiency (72.42±0.013), a sustained drug release for a period of 24 h. The pharmacokinetic profile of the drug from microbeads exhibited an enhanced oral bioavailability (2.4 times higher than that of pure drug), lower elimination rate (1.14 times lesser for the drug in microbeads) with prolonged elimination half-life (2.561 times higher than pure zaltoprofen). Conclusion: Zaltoprofen entrapped microbeads demonstrated as a better delivery system for the sustained release of drug and also to circumvent the drawbacks associated with conventional therapy

Ameliorating the antitumor activity of lenalidomide using PLGA nanoparticles for the treatment of multiple myeloma

Abstract Lenalidomide (LND) is an anti-cancer drug and an effective derivative of thalidomide used for multiple myeloma therapy. Because of its poor solubility in water, LND is known to cause low oral bioavailability (below 33%), and as a direct consequence of this, the dosing frequency is extended thus increasing risk of toxicity. To improve its bioavailability and sustained release, the present study aims to formulate polymeric nanoparticles (NPs) for LND using [Poly (lactic-co-glycolic acid)] (PLGA) as a polymer. The polymeric NPs were evaluated for particle size, SEM, XRD, drug content, entrapment efficiency (EE), in vitro release studies and in vivo bioavailability studies in rats. The formulated NPs possessed a size of 179±0.9 nm and a zeta potential of -24.4 ± 0.2 mV. The drug loading and EE of the optimized formulation was 32 ± 0.37 % and 78 ± 0.92% respectively. After oral administration of LND PLGA-NPs, the relative bioavailability was enhanced about 3.67-fold compared to LND. This study demonstrates the novel drug delivery for LND with PLGA-NPs as effective drug delivery system for sustained delivery of LND

Ameliorating the antitumor activity of lenalidomide using PLGA nanoparticles for the treatment of multiple myeloma

Abstract Lenalidomide (LND) is an anti-cancer drug and an effective derivative of thalidomide used for multiple myeloma therapy. Because of its poor solubility in water, LND is known to cause low oral bioavailability (below 33%), and as a direct consequence of this, the dosing frequency is extended thus increasing risk of toxicity. To improve its bioavailability and sustained release, the present study aims to formulate polymeric nanoparticles (NPs) for LND using [Poly (lactic-co-glycolic acid)] (PLGA) as a polymer. The polymeric NPs were evaluated for particle size, SEM, XRD, drug content, entrapment efficiency (EE), in vitro release studies and in vivo bioavailability studies in rats. The formulated NPs possessed a size of 179±0.9 nm and a zeta potential of -24.4 ± 0.2 mV. The drug loading and EE of the optimized formulation was 32 ± 0.37 % and 78 ± 0.92% respectively. After oral administration of LND PLGA-NPs, the relative bioavailability was enhanced about 3.67-fold compared to LND. This study demonstrates the novel drug delivery for LND with PLGA-NPs as effective drug delivery system for sustained delivery of LND

Pelletization by Extrusion-Spheronization- A detailed review

Oral multiparticulate drug system (e.g. pellets, granules) in comparison to single unit dosage form offer biopharmaceutical advantages in terms of more even and predictable drug distribution in enteric system. Extrusion spheronization is one of the most commonly used techniques in the formulation of such multiparticulate beads and pellets providing sustained and controlled release or modified release drug delivery. This review outlines the various steps involved in the extrusion spheronization process, the excipients used in such formulations along with some modifications and various processing variables affecting the quality of pellets formed. In addition, an overview of the methods available for the quality check of the pellets is reviewed

Formulation of Sodium Alginate Nanospheres Containing Amphotericin B for the Treatment of Systemic Candidiasis

Purpose: The aim of this work was to formulate sodium alginate nanospheres of amphotericin B by controlled gellification method and to evaluate the role of the nanospheres as a "passive carrier" in targeted antifungal therapy. Methods: Sodium alginate nanospheres of amphotericin B were prepared by controlled gellification method, and the particle size analysis was carried out by scanning electron microscopy. The carrier capacity of sodium alginate was evaluated in terms of drug to polymer ratio. In vitro release study was carried out on all drug loaded nanospheres by the dialysis method. Release kinetics of drug from different drug loaded nanospheres was also determined. The in vivo antifungal efficacy of nanospheres bound drug vis-à-vis the free drug was evaluated in candidiasis- induced mice models. Results: Preparation of nanospheres through controlled gellification method yielded particles with a size range of 419.6 ± 0.28 nm. Studies on drug to polymer ratio showed a linear relationship between concentration of drug and drug loading capacity. In vitro release kinetic study revealed that the release of drug from the nanospheres followed Fickian diffusion. In vivo studies showed that the nanospherebound drug produced a higher antifungal efficacy than the free drug. Conclusion: The formulated sodium alginate nanospheres containing amphotericin B was found to have better antifungal activity when compared to the free drug and also yielded sustained in vitro release

CHRONOTHERAPEUTIC DRUG DELIVERY SYSTEM: AN EMERGING APPROACH TO TREAT CIRCADIAN RHYTHMIC RELATED DISEASE

The research on chronotherapy has garnered interest from scientists to understand circadian rhythms and their applications in the biological system. The area of chronotherapeutics covers essential information which is helpful to move forward and solve entanglements in current drug delivery technology. Chronotherapy is the conveying drugs in the body at the target site by maintaining perfect synchronicity with circadian rhythms. The main aim of the current rhythmic research is to formulate and design a therapeutic novel system which can deliver the drug in a desired way inside the body to treat various rhythmic diseases according to their occurrence. Drug release from an ideal chronotherapeutic system should be rapid, and the release of drug from the delivery system should also be complete after a specific or defined lag time period. Recently, scientists are involved in developing chronotherapeutic drug delivery system to treat chronological diseases such as single and multiple units using an erodible, soluble or insoluble polymer coating, and stimuli regulated drug delivery systems. In this review, we focus on the elaboration of the concept of chronotherapy, main challenges ahead during its development process, current approaches and its future applications in drug delivery in the treatment of circadian rhythmic diseases

Pelletization by Extrusion-Spheronization- A detailed review

Oral multiparticulate drug system (e.g. pellets, granules) in comparison to single unit dosage form offer biopharmaceutical advantages in terms of more even and predictable drug distribution in enteric system. Extrusion spheronization is one of the most commonly used techniques in the formulation of such multiparticulate beads and pellets providing sustained and controlled release or modified release drug delivery. This review outlines the various steps involved in the extrusion spheronization process, the excipients used in such formulations along with some modifications and various processing variables affecting the quality of pellets formed. In addition, an overview of the methods available for the quality check of the pellets is reviewed

EMERGING TRENDS IN STIMULI-SENSITIVE DRUG DELIVERY SYSTEM: A COMPREHENSIVE REVIEW OF CLINICAL APPLICATIONS AND RECENT ADVANCEMENTS

The combination of fields such as applied physics, biology, computational modeling and analysis, pharmaceuticals, chemistry, optics, and material science study has been made easier for the rise of stimuli-sensitive drug delivery systems. This study aimed to overcome the shortcomings of conventional therapeutic approaches by concentrating on the most recent developments in stimuli-sensitive drug delivery systems, which are intended to accomplish the targeted release of drugs in specified areas. This review aims to provide an overview of stimuli-sensitive drug delivery systems and recent advancements between 2015 and 2023 by focusing on their ability to respond to exogenous and endogenous stimuli. In recent years, significant progress has been made in developing innovative stimuli-responsive drug delivery platforms that can trigger various external stimuli, such as light, temperature, magnetic fields, and ultrasound. These exogenous stimuli-responsive systems enable on-demand drug release at specific target sites, allowing for personalized and patient-centric treatment strategies. Notable breakthroughs include photoresponsive nanocarriers, thermosensitive hydrogels, and magnetic nanoparticles, all designed to respond to specific cues for controlled drug delivery