Chitosan and neem gum-based polyelectrolyte complex for design of allantoin loaded biocomposite film: In-vitro, ex-vivo, and in-vivo characterization.

Presently, the preference for chitosan (CS) and gum polysaccharides in biomedical applications including drug delivery and wound healing has been extensively documented. Despite this, the demerits of CS and gum polysaccharides such as poor mechanical properties, degradation rate, swelling, etc., limit their applications for designing biocomposite films for drug delivery. Therefore, the anticipated work aims to design a CS and neem gum polysaccharides (NGP) polyelectrolyte complex-based allantoin (AT)-loaded (CS/NGP-AT) biocomposite film for improved wound healing. In brief, CS, NGP, and CS/NGP-AT-based biocomposite films were prepared using the solvent-casting method, and in-vitro, ex-vivo, and in-vivo characterizations were performed to assess the performance of these biocomposite films compared to their counterparts. In this, diffractogram and thermogram analysis assured the conversion of crystalline AT into an amorphous form. The optimized CS/NGP/AT-3 formulation exhibited controlled water absorption, appropriate water uptake capacity, good water retention ability, excellent water vapor transmission rate, controlled degradation rate, enhanced mechanical properties, cell and blood biocompatibility, etc. Furthermore, it offered improved antimicrobial, anti-inflammatory, and antioxidant potential. The optimized film provided a modified release (88.3 ± 0.3 %) of AT from the film for up to 48 h. Wound healing experiments on rats and their histopathology studies confirmed a significantly higher rate of wound recovery within 14 days compared to the control and CS/NGP film, attributable to the combined effects of CS, NGP, and AT. In conclusion, the fabricated CS/NGP-based biocomposite film presents promising prospects as an excellent candidate for wound healing applications.

Design of polyacrylamide grafted sesbania gum-mediated pH-responsive IPN-based microbeads for delivery of diclofenac sodium: In-vitro-in-vivo characterizations.

Microwave-assisted grafting of polyacrylamide on sesbania gum (PAAM-g-SG) was implemented employing a 32 full factorial experimental design and was hydrolyzed using sodium hydroxide (NaOH) to form H-PAAM-g-SG. Further, the diclofenac sodium-loaded novel pH-sensitive interpenetrating polymeric network (IPN) microbeads were designed using an optimized H-PAAM-g-SG and sodium alginate (SA). Different spectroscopic analysis including FTIR spectroscopy, 1H NMR spectroscopy, elemental analysis, thermal analysis, etc. was performed to confirm the synthesis of PAAM-g-SG and diclofenac-loaded pH-sensitive IPN H-PAAM-g-SG-SA microbeads. Here, Ca+2 ions combine with two strands of SA and form a round-shape structure that encloses uncross-linked H-PAAM-g-SG polymer and diclofenac sodium. As well, glutaraldehyde (GL) addition improved the mechanical strength due to acetal structure between hydroxyl of H-PAAM-g-SG and aldehyde of GL. The drug entrapment was confirmed proportional relationship to the Ca+2 ions concentration whereas an increase in GL concentration resulted in a reduced drug entrapment. The pH pulsatile study assured the reversible swelling-shrinkage behavior of IPN microbeads due to the carboxyl group of PAAM-g-SG. The drug release from H-PAAM-g-SG-SA microbeads (batch: S9) was found to be 84.21 % (12h) which was non-significant (p > 0.05; f2 = 79 âˆ¼ 90) over marketed formulation (83.31 %). Moreover, it follows the Korsmeyer Peppas (R2 = 0.996) as the best-fit release kinetic model. The pH-sensitive release of diclofenac sodium from IPN H-PAAM-g-SG-SA microbeads was assured based on in vivo anti-inflammatory activity (p < 0.05). Therefore, developed novel pH-sensitive IPN microbeads based on H-PAAM-g-SG are a promising polymeric carrier substitute for delivery of drugs actuated by a pH stimulus.

Formulation, optimization, and in-vitro-ex-vivo evaluation of dual-crosslinked zinc pectinate-neem gum-interpenetrating polymer network mediated lansoprazole loaded floating microbeads.

Low methoxy pectin (LM pectin) suffers from burst release owing to its high swellability and solubility in water. Consequently, in ways to design an ideal drug delivery system, these obstacles must be surmounted. Therefore, the work aimed to design dual crosslinked LM pectin -neem gum (NG) mediated interpenetrating polymer network (IPN) floating mucoadhesive microbeads for lansoprazole (LNZ) gastro-retentive delivery. In short, LNZ-loaded floating microbeads were achieved by using the ionic gelation method wherein zinc acetate was preferred as a crosslinking agent. The optimization of IPN microbeads was performed employing a 32factorial design wherein concentration of pectin and NG was considered as independent factors whereas dependant factors are entrapment efficiency and drug release. Importantly, carboxylic functionality of low methoxy (LM) pectin and hydroxylic functionality NG cross-linked with Zn+2 forms a 3D network. Diffractogram and thermogram revealed that conversion of drug from crystalline to amorphous form because of entrapment of drug within polymeric network. Anticipated floating microbeads showed that polymer concentration had considerable effect on drug encapsulation efficiency and drug release. Briefly, optimizing floating microbeads (Batch B:5) showed maximum drug entrapment (87.47 %) with a delayed drug release (69.20 %, at 8 h) due to formation of strong IPN. Moreover, it showed good mucoadhesive aptitude with goat stomach mucosa because of entanglement between gum and mucus layer. In addition, use of calcium silicate assists to modulate floating profile of IPN microbeads. Therefore, designing dual crosslinked zinc-pectinate-NG mediated IPN floating mucoadhesive microbeads will offer a new substitute for floating delivery.

Preparation, Characterization and In Vivo Assessment of Repaglinide Nanosuspension for Oral Bioavailability Improvement.

AIMS AND BACKGROUND: The objective of the study was to improve the bioavailability of poorly soluble repaglinide (RPG) by preparing nanosuspension with poloxamer 188 using high pressure homogenization (HPH). The recent patents on nanocrystals (US20150337006A1) facilitated selection of drug and polymer. METHODS: Suspensions containing dissimilar sized particles were prepared by ultrasonication and HPH. The prepared aqueous suspensions were lyophilized and then characterized. Further, the dried aqueous suspensions were evaluated for drug content, solubility, in vitro dissolution, oral bioavailability study and stability study. RESULTS: RPG nanoparticles size, polydispersity index (PDI) and zeta potential were found to be 280.8 ± 15 nm, 0.279 ± 0.04 and - 25.81 ± 1.6mV, respectively. DSC and XRD results showed that RPG particles in aqueous suspensions were present in a crystalline state; however, RPG nanoparticles exhibited decreased lattice energy due to smaller particle size. Nanoparticles prepared by HPH exhibited significant improvements in solubility and dissolution rate. Oral bioavailability was found to be enhanced by 1.93 fold in comparison with that of plain RPG. The nanosuspension was found to be stable when stored at 5°C ± 3°C. CONCLUSION: The outcomes of the study revealed significant enhancement in dissolution rate and oral bioavailability of RPG due to size reduction to nano range by HPH.

Aripiprazole-Loaded Polymeric Micelles: Fabrication, Optimization and Evaluation using Response Surface Method.

AIMS AND BACKGROUND: The fundamental objective of current study was to encapsulate Aripiprazole (ARP) within Pluronic F127 micelles to improve its aqueous solubility. The recent patents on Aripiprazole (JP2013136621) and micelles (WO2016004369A1) facilitated selection of drug and polymer. MATERIALS AND METHODS: The drug-laden micelles were fabricated using thin-film hydration technique. Optimization of the micellar formulation was done by using response surface method (RSM). The Pluronic F127 concentration of 150 mg and 75 rpm rotational speed of rotary evaporator were found to be optimized conditions for formulating micelles. RESULTS: The prepared batches were further characterized for PDI (polydispersity index), zeta potential, % DLC (% Drug loading content), % EE (% Entrapment Efficiency) and % drug release study; results of these parameters were found to be 0.228, -4.04 mV and 76.50 % and 18.56 % respectively. It was observed from the In vitro release study that 97.37 ± 1.81 % drug had released from micelles after 20h which were found about thrice as compared to that of pure drug. The optimized ARP micellar formulation was characterized using DSC (Differential Scanning Colorimetry), FT-IR (Fourier Transformed Infrared Spectroscopy), P-XRD (Powdered X-ray Diffraction Study) and TEM (Transmission Electronic Microscopy) studies. ARP-loaded micelles displayed a hydrodynamic diameter of 170.3 nm and a sphere-shaped morphology as determined by dynamic light scattering as well as TEM study. CONCLUSION: It is concluded that the prepared polymeric micellar system has an excellent potential to be used as a delivery carrier for Aripiprazole with increased solubility.

Preparation, characterization and in vivo evaluation of antihyperglycemic activity of microwave generated repaglinide solid dispersion.

The influence of microwave technology on the in vitro dissolution rate and in vivo antihyperglycemic activity of a poorly water soluble drug, repaglinide (RG) was studied. Solid dispersions were prepared by conventional fusion method and microwave method using poloxamer 188. The dispersions were characterized by solubility study, dissolution study, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). Microwave generated solid dispersions exhibited remarkable improvement in solubility and dissolution rate compared to that of pure RG. Results of DSC, XRD and SEM study showed conversion of crystalline form of RG to amorphous form. In vivo studies revealed that the microwave generated solid dispersion showed significant improvements in antihyperglycemic activity as compared to RG alone, thus confirming the advantage of improved pharmacological activity of RG by microwave method. In conclusion, microwave method could be considered as simple, efficient and solvent free promising alternative method to prepare solid dispersion of poorly water soluble drug RG with significant enhancement in solubility, dissolution rate and antihyperglycemic activity.