Novel Drug Delivery Systems of Resveratrol to Bioavailability and Therapeutic Effects

Resveratrol is a naturally occurring product used in the prevention and treatment of various diseases by acting as a potent defensive antioxidant. Resveratrol can be used in various fields, but the use is limited due to its poor solubility and hence low bioavailability. For overcoming this limitation, various drug delivery systems of resveratrol were developed. The aim of the novel drug delivery system (NDDS) is to provide a therapeutic amount of drug to the target site to maintain the desired drug concentration. NDDS enhances the duration of therapeutic activity, increases plasma half-life, decreases the immunogenicity, increases the stability of biopharmaceuticals, improves the solubility of low molecular weight drugs so does the bioavailability, and has a potential of targeted drug delivery. However, they have their own advantages as well as limitations. This chapter focuses on: (1) general introduction to resveratrol and its various therapeutic uses, (2) pharmacokinetic- and bioavailability-related problems of resveratrol, and (3) general about various NDDS used in resveratrol formulations

NOVEL RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS ESTIMATION OF SAXAGLIPTIN AND GLIMEPIRIDE

Objective: The objective of the present study was to develop, and validate a novel reverse phase high performance liquid chromatographic (RP-HPLC) method, for simultaneous determination of saxagliptin (SAXA) and glimepiride (GLIM), in bulk mixtures, and in tablets.Methods: Determination of the drugs, SAXA and GLIM, was carried out employing ODS C18 column (250 mm X 4.6 mm i. d, 5 µm particle size), with diode array detector at λmax of 230 nm. The mobile phase employed for the current study, composed of two solvents, i.e., A (acetonitrile), and B (0.1 % w/v sodium di-hydrogen orthophosphate buffer, pH 3.8 adjusted with orthophosphoric acid). The mobile phase was pumped at a flow rate of 0.75 ml/min in the gradient mode. The validation study with respect to specificity, linearity, precision, accuracy, robustness, limit of detection (LOD), and limit of quantification (LOQ), was carried out employing the ICH Guidelines.Results: The developed method was selective and linear for both the drugs, i.e., between 15.63 µg/ml and 250.00 µg/ml for SAXA, and 7.81 µg/ml and 125.00 µg/ml for GLIM, with a correlation coefficient (R2) 0.9977 and 0.9982, for SAXA, and GLIM, respectively. The % recovery obtained was 102.98±0.14% for SAXA, and 101.84±1.96% for GLIM. The LOD and LOQ values for SAXA were obtained to be 1.30 µg/ml, and 3.94 µg/ml, respectively, while for GLIM, LOD was 0.82 µg/ml and LOQ was 2.48 µg/ml. The method also exhibits good robustness for different chromatographic conditions like wavelength, flow rate, mobile phase and injection volume.Conclusion: The method was successfully employed, for the quantification of SAXA and GLIM, in the quality control of in-house developed tablets, and can be applied for the industrial use

Efficacy of resveratrol encapsulated microsponges delivered by pectin based matrix tablets in rats with acetic acid-induced ulcerative colitis

Objectives: The objective of the present work to encapsulate the resveratrol (RES) inside the chitosan-based microsponges, employing the systematic optimization by 33 Box-Behnken design for the colonic targeting.Significance: Enhanced therapeutic efficacy of RES-loaded microsponges and matrix tablets, vis-a-vis pureRES for ulcerative colitis.Methods: RES-loaded microsponges were prepared employing the systematic optimization by 33 Box-Behnken design for the colonic targeting. The best-optimizedRES-loaded microsponge was compressed in the form of a tablet, employing pectin as a matrix-forming material. The encapsulation of RES inside microsponge was confirmed by XRD, DSC and FT-IR. Further, both RES-loaded microsponges and matrix tablets were evaluated for in vitro release kinetics and further evaluated for in vivo ulcerative colitis animal model.Results: Optimization experiments was obtained as the high value of r2 (particle size = 0.9999; %EE = 0.9652; %CDR = 0.9469) inferred excellent goodness of fit. SEM revealed nearly spherical and porous nature of RES-loaded microsponges. The in vitro release kinetic showed zero-order release for RES-loaded microsponges and Korsmeyer-Peppas model for matrix tablets. The pharmacodynamic studies, in ulcerative colitis rat model, indicated better therapeutic efficacy of drug-loaded microsponges and matrix tablets, vis-a-vis pure RES. Thus, the present study advocates the potential of RES based microsponges delivered by pectin based matrix tablet, in the treatment of various colonic disorders.Conclusion: The present study proved that RES-loaded microsponges and matrix tablets based on chitosan and pectin can be the ideal delivery system for colonic delivery of RES

Nanocarriers: more than tour de force for thymoquinone

Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers

Azelaic acid and Melaleuca alternifolia essential oil co-loaded vesicular carrier for combinational therapy of acne

Aim: Azelaic acid (AzA), a comedolytic, antibacterial, anti-inflammatory anti-melanogenic agent, prescribed against acne vulgaris is safe on skin. Its combination with another widely used anti-acne agent, tea tree oil (EO) whose delivery is limited by volatility, instability and lipophilicity constraints was attempted. Method: Solvent injection was used to prepare AzA-EO integrated ethosomes. Result: Ethosomes were transformed into carbopol hydrogel, which exhibited pseudo-plastic properties with appreciable firmness, work of shear, stickiness and work of adhesion. The hydrogel showed better permeation and retention characteristics vis-a-vis commercial formulation (AzidermTM), when evaluated in Wistar rat skin. Further, ethosome hydrogel composite was better tolerated with no side effects. Conclusion: The findings suggests that the aforementioned strategy could be a potential treatment used for acne management. </jats:p

Hydrogel composite containing azelaic acid and tea tree essential oil as a therapeutic strategy for Propionibacterium and testosterone-induced acne.

Azelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index  90%), and negative zeta potential (-1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris

Gastric ulcer healing by chebulinic acid solid dispersion-loaded gastroretentive raft systems: preclinical evidence

Background: Chebulinic acid (CA), a component in Terminalia chebula, exhibits antiulcer activity, but has poor aqueous solubility. Raft-forming systems incorporating solid dispersions (SDs) of CA, were developed to overcome its poor biopharmaceutical properties and to prolong the gastric residence time for maximum activity. Methods: SDs were formulated by a solvent evaporation method using Eudragit EPO. Raft formulations consisted of sodium alginate as a polymer. Results: Release of CA in the dissolution medium was 40%, whereas SDs showed 95.45% release. The CA raft system (20 mg/kg) showed curative efficacy in an alcohol-induced gastric ulcer model and increased protection when compared with omeprazole (10 mg/kg) and CA suspension (20 mg/kg). Conclusion: These studies demonstrated SD raft systems to be a promising approach for antiulcer therapy by CA. </jats:p

Hydrogel composite containing azelaic acid and tea tree essential oil as a therapeutic strategy for Propionibacterium and testosterone-induced acne

AbstractAzelaic acid (AzA) is a USFDA bioactive prescribed against acne vulgaris. It possesses delivery challenges like poor aqueous solubility, low skin-penetrability, and dose-dependent side effects, which could be overcome by its synergistic combination with tea tree oil (TTO) as a microemulsion (ME)-based hydrogel composite. AzA-TTO ME was prepared to employ pseudo-ternary phase diagram construction. The best AzA-TTO ME was of uniform size (polydispersity index &lt; 0.7), nano-range (~357.4 ± 2% nm), transmittance (&gt; 90%), and negative zeta potential (−1.42 ± 0.25% mV) values. ME hydrogel composite with optimum rheological and textural attributes showed better permeation, retention, and skin-compliant characteristics, vis-a-vis marketed formulation (Aziderm™) when evaluated in Wistar rat skin. In vitro antibacterial efficacy in bacterial strains, i.e., Staphylococcus aureus, Propionibacterium acne, and Staphylococcus epidermidis, was evaluated employing agar well plate diffusion and broth dilution assay. ME hydrogel has shown an increase in zone of inhibition by two folds and a decrease in minimum inhibitory concentration (MIC) by eightfold against P. acnes vis-a-vis AzA. Finally, ME hydrogel composite exhibited a better reduction in the papule density (93.75 ± 1.64%) in comparison to Aziderm™ 72.69 ± 4.67%) on acne as developed in rats by inducing testosterone. Thus, the developed AzA-TTO ME hydrogel composite promises an efficacious and comparatively safer drug delivery system for the topical therapy of acne vulgaris. Graphical abstract</jats:p

Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: optimization, characterization, pharmacokinetic, and hepatotoxicity studies

Thymoquinone (TQ) is an antioxidant, anti-inflammatory, and hepatoprotective compound obtained from the black seed oil of Nigella sativa. However, high hydrophobicity, instability at higher pH levels, photosensitivity, and low oral bioavailability hinder its delivery to the target tissues. A self-nanoemulsifying drug delivery system (SNEDDS) was fabricated using the microemulsification technique to address these issues. Its physicochemical properties, thermodynamic stability studies, drug release kinetics, in vivo pharmacokinetics, and hepatoprotective activity were evaluated. The droplet size was in the nano-range (< 90 nm). Zeta potential was measured to be -11.35 mV, signifying the high stability of the oil droplets. In vivo pharmacokinetic evaluation showed a fourfold increase in the bioavailability of TQ-SNEDDS over pure TQ. Furthermore, in a PCM-induced animal model, TQ-SNEDDS demonstrated significant (p < 0.05) hepatoprotective activity compared to pure TQ and silymarin. Reduction in liver biomarker enzymes and histopathological examinations of liver sections further supported the results. In this study, SNEDDS was demonstrated to be an improved oral delivery method for TQ, since it potentiates hepatotoxicity and enhances bioavailability