ENHANCEMENT OF SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS-II AMBRISENTAN: IN VITRO, IN VIVO AND EX VIVO ANALYSIS

Objective: The aim of this investigation was to enhance the solubility and bioavailability of the BCS class II poorly water-soluble drug ambrisentan by solid dispersion (SD) techniques using Gelucire 50/13 as a hydrophilic carrier. Methods: Solid dispersion of ambrisentan was prepared by kneading method using different dug: carrier ratios. Prepared SD was characterized for solubility, drug content, percentage yield, in vitro dissolution, ex vivo permeation and bioavailability. Solid-state characterization was performed by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Results: All the SDs formulations showed increase in drug solubility and dissolution when compared with its pure form. Aqueous solubility of the drug was found to be increased 8.23 fold in SD. DSC study showed that endothermic peak of the drug was disappeared in spectra of SD, confirming its amorphous conversion, XRD study revealed the reduction to almost absence of specific high-intensity peaks of drug which confirmed the reduction of crysatallinity of ambrisentan in SD. SEM of optimized SD formulation demonstrates the complete encapsulation and solubilization drug. In vitro dissolution study showed that optimized SD formulation (ASD4) gives the faster drug release of 101.5% in 60 min, as compare to its pure form and other SD formulations. Conclusion: Solid dispersion ASD4 prepared with 1:4 drug to carrier ratio showed the highest drug solubility and in vitro dissolution. The ex vivo and in vivo studies performed on optimized formulation ASD4 showed enhancement in drug permeability and bioavailability in Gelucire 50/13 based SD formulation.

Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics

Many gaps exist in our understanding of species differences in gastrointestinal (GI) fluid composition and the associated impact of food intake and dietary composition on in vivo drug solubilization. This information gap can lead to uncertainties with regard to how best to formulate pharmaceuticals for veterinary use or the in vitro test conditions that will be most predictive of species-specific in vivo oral product performance. To address these challenges, this overview explores species-specific factors that can influence oral drug solubility and the formulation approaches that can be employed to overcome solubility-associated bioavailability difficulties. These discussions are framed around some of the basic principles associated with drug solubilization, reported species differences in GI fluid composition, types of oral dosage forms typically given for the various animal species, and the effect of prandial state in dogs and cats. This basic information is integrated into a question-and-answer section that addresses some of the formulation issues that can arise in the development of veterinary medicinals.

Current Perspectives on Nanoemulsions in Targeted Drug Delivery

Nanoemulsions are an isotropical mixture of oil, surfactant, and water with droplet diameter approximately in the range of 10-100 nm. They are being exponentially used for drug delivery systems for the influential administration of therapeutical agents because of their potential advantages over other approaches. Nanoemulsions can be used to design delivery systems that have increased drug loading, enhanced drug solubility, increased bioavailability, controlled drug release, and enhanced protection against chemical or enzymatic degradation. Moreover, nanoemulsions have better thermodynamical stability to flocculation, sedimentation, and creaming than conventional emulsions. Their small droplet dimensions and large droplet surface area positively influence drug transport and delivery, along with allowing targeting to specific sites. This chapter focuses on recent applications of nanoemulsions in the area of drug delivery.

Theoretical consideration of solubility by Hildebrand solubility approach

Pharmaceutical field is widely focusing on solubility parameter models to select solvent or non-solvent that can enhance solvency of drug. Solubility Parameter is very useful concept in understanding the mechanism of solvent and solvency behavior with their applications in pharmaceuticals to open the door of research having focus on theoretical considerations of solubility. Hildebrand and Hansen Solubility Parameter are frequently used to identify solvents.

Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer

The drug-loaded nanocarriers have overcome various challenges compared with the pure chemotherapeutic drug, such as limited bioavailability, multiple drug resistance, poor patient compliance, and adverse drug reactions, offering advantages such as protection from degradation in the blood stream, better drug solubility, and improved drug stability. One promising group of controlled and targeted drug delivery systems is polymer-based nanoparticles that can sustain the release of the active agent by diffusion and their degradation. Sorafenib is the only drug that can prolong the life of patients suffering from hepatocellular carcinoma. Cisplatin remains one of the most widely used broad-spectrum anticancer drugs for the treatment of a variety of solid tumours. Nanoformulations can exert a synergistic effect by entrapping two drugs with different modes of action, such as sorafenib and cisplatin. In our study, polymeric nanoparticles were prepared with a good production yield by an improved double emulsion solvent evaporation method using the copolymer of 12-hydroxystearic acid with ε-caprolactone (12CL), a biocatalytically synthesised biocompatible and biodegradable carrier, for the co-entrapment of sorafenib and cisplatin in nanotherapeutics. A bovine serum albumin (BSA) model compound was used to increase the cisplatin incorporation; then, it was successfully substituted by a iRGD tumour penetrating peptide that might provide a targeting function of the nanoparticles.

Deep Eutectic Solvents as Active Pharmaceutical Ingredient Delivery Systems in the Treatment of Metabolic Related Diseases

Metabolic related diseases such as cancer, diabetes mellitus and atherosclerosis are major challenges for human health and safety worldwide due to their associations with high morbidity and mortality. It is of great significance to develop the effective active pharmaceutical ingredient (API) delivery systems for treatment of metabolic diseases. With their unique merits like easy preparation, high adjustability, low toxicity, low cost, satisfactory stability and biodegradation, deep eutectic solvents (DESs) are unarguably green and sustainable API delivery systems that have been developed to improve drug solubility and treat metabolic related diseases including cancer, diabetes mellitus and atherosclerosis. Many reports about DESs as API delivery systems in the therapy of cancer, diabetes mellitus and atherosclerosis exist but no systematic overview of these results is available, which motivated the current work.

Collagen Nanoparticles in Drug Delivery Systems and Tissue Engineering

The versatile natural polymer, collagen, has gained vast attention in biomedicine. Due to its biocompatibility, biodegradability, weak antigenicity, biomimetics and well-known safety profile, it is widely used as a drug, protein and gene carrier, and as a scaffold matrix in tissue engineering. Nanoparticles develop favorable chemical and physical properties such as increased drug half-life, improved hydrophobic drug solubility and controlled and targeted drug release. Their reduced toxicity, controllable characteristics of scaffolds and stimuli-responsive behavior make them suitable in regenerative medicine and tissue engineering. Collagen associates and absorbs nanoparticles leading to significant impacts on their biological functioning in any biofluid. This review will discuss collagen nanoparticle preparation methods and their applications and developments in drug delivery systems and tissue engineering.

Measurement and modeling of clemastine fumarate (antihistamine drug) solubility in supercritical carbon dioxide

The solubilities of clemastine fumarate in supercritical carbon dioxide (ScCO2) were measured for the first time at temperature (308 to 338 K) and pressure (12 to 27 MPa). The measured solubilities were reported in terms of mole faction (mol/mol total) and it had a range from 1.61 × 10–6 to 9.41 × 10–6. Various models were used to correlate the data. The efficacy of the models was quantified with corrected Akaike’s information criterion (AICc). A new cluster salvation model was derived to correlate the solubility data. The new model was able to correlate the data and deviation was 10.3% in terms of average absolute relative deviation (AARD). Furthermore, the measured solubilities were also correlated with existing K.-W. Chen et al., model, equation of state model and a few other density models. Among density models, Reddy and Garlapati model was observed to be the best model and corresponding AARD was 7.57% (corresponding AICc was − 678.88). The temperature independent Peng–Robinson equation of state was able to correlate the data and AARD was 8.25% (corresponding AICc was − 674.88). Thermodynamic parameters like heats of reaction, sublimation and solvation of clemastine fumarate were calculated and reported.

Co-Loading of Temozolomide and Curcumin into a Calix[4]arene-Based Nanocontainer for Potential Combined Chemotherapy: Binding Features, Enhanced Drug Solubility and Stability in Aqueous Medium

The co-delivery of anticancer drugs into tumor cells by a nanocarrier may provide a new paradigm in chemotherapy. Temozolomide and curcumin are anticancer drugs with a synergistic effect in the treatment of multiform glioblastoma. In this study, the entrapment and co-entrapment of temozolomide and curcumin in a p-sulfonato-calix[4]arene nanoparticle was investigated by NMR spectroscopy, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. Critical micellar concentration, nanoparticle size, zeta potential, drug loading percentage, and thermodynamic parameters were all consistent with a drug delivery system. Our data showed that temozolomide is hosted in the cavity of the calix[4]arene building blocks while curcumin is entrapped within the nanoparticle. Isothermal titration calorimetry evidenced that drug complexation and entrapment are entropy driven processes. The loading in the calixarene-based nanocontainer enhanced the solubility and half-life of both drugs, whose medicinal efficacy is affected by low solubility and rapid degradation. The calixarene-based nanocontainer appears to be a promising new candidate for nanocarrier-based drug combination therapy for glioblastoma.