Amorphous systems for delivery of nutraceuticals: challenges opportunities.

Amorphous solid products have recently gained a lot of attention as key solutions to improve the solubility and bioavailability of poorly soluble nutraceuticals. A pure amorphous drug is a high-energy form; physically/chemically unstable and so easily gets recrystallized into the less soluble crystalline form limiting solubility and bioavailability issues. Amorphous solid dispersion and co-amorphous are new formulation approach that stabilized unstable amorphous form through different mechanisms such as preventing mobility, high glass transition temperature and molecular interaction. Nutraceuticals have been received the utmost importance due to their health benefits. However, most of these compounds have been associated with poor oral bioavailability due to poor solubility, high lipophilicity, high melting point, poor permeability, degradability and rapid metabolism in the gastrointestinal tract (GIT) which limits its health benefits. This review provides us a systematic application of amorphous systems to the delivery of poorly soluble nutraceuticals, with the aim of overcoming their pharmacokinetic limitations and improved pharmacological potential. In particular, it describes the challenges associated with delivery of oral nutraceuticals, various methods involved in the preparation and characterization of amorphous systems and permeability enhancement of nutraceuticals are in detail.

Budding Multi-matrix Technology-a Retrospective Approach, Deep Insights, and Future Perspectives.

The human race is consistently striving for achieving good health and eliminate disease-causing factors. For the last few decades, scientists have been endeavoring to invent and innovate technologies that can substitute the conventional dosage forms and enable targeted and prolonged drug release at a particular site. The novel multi-matrix technology is a type of matrix formulation where the formulation is embraced to have a matrix system with multiple number of matrices. The MMX technology embraces with a combination of outer hydrophilic layer and amphiphilic/lipophilic core layer, within which drug is encapsulated followed by enteric coating for extended/targeted release at the required site. In comparison to conventional oral drug delivery systems and other drug delivery systems, multi-matrix (MMX) technology formulations afford many advantages. Additionally, it attributes for targeting strategy aimed at the colon and offers modified prolonged drug release. Thus, it has emerged rapidly as a potential alternative option in targeted oral drug delivery. However, the development of this MMX technology formulations is a exigent task and also has its own set of limitations. Due to its promising advantages and colon targeting strategy over the other colon targeted drug delivery systems, premier global companies are exploiting its potential. This article review deep insights into the formulation procedures, drug delivery mechanism, advantages, limitations, safety and efficacy studies of various marketed drug formulations of MMX technology including regulatory perspectives and future perspectives.

Design and Development of Repaglinide Microemulsion Gel for Transdermal Delivery.

Microemulsion formulation of repaglinide, a BCS class II hypoglycemic agent with limited oral bioavailability, was developed considering its solubility in various oils, surfactants, and cosurfactants. The pseudo-ternary phase diagrams for microemulsion regions were constructed by water titration method at K m 1:1 and characterized for optical birefringence, percentage transmittance, pH, refractive index, globule size, zeta potential, viscosity, drug content, and thermodynamic stability. To enhance the drug permeation and residence time, the optimized microemulsions having mean globule size of 36.15 ± 9.89 nm was gelled with xanthan gum. The developed microemulsion-based gel was characterized for globule size, zeta potential, pH, and drug content. All evaluation parameters upon gelling were found to be satisfactory. Ex vivo permeability study across rat skin demonstrated higher steady-state flux (P < 0.05) for microemulsion of repaglinide in comparison to the repaglinide microemulsion gel. At the end of 24 h, the cumulative drug permeation from microemulsion and microemulsion gel was found to be 229.19 ± 24.34 and 180.84 ± 17.40 µg/cm2, respectively. The microemulsion formulation showed 12.30-fold increase in flux as compared to drug suspension with highest enhancement ratio (E r ) of 12.36. Whereas microemulsion gel exhibited 10.97-fold increase in flux (with highest E r , 11.78) as compared to repaglinide (RPG) suspension. In vivo efficacy study was performed in normal Sprague-Dawley rats by using oral glucose tolerance test. Results of RPG transdermal microemulsion gel demonstrated remarkable advantage over orally administered RPG by reducing the glucose level in controlled manner. Hence, it could be a new, alternative dosage form for effective therapy of type 2 diabetes mellitus.

An updated review on exosomes: biosynthesis to clinical applications.

Exosomes are membrane-based extracellular vesicles naturally released by the cells. Nano size range of exosomes and unique properties such as stability, biocompatibility and low immunogenicity are key parameters, which make them suitable as nanoparticulate drug delivery system and also considered as promising delivery carriers for future clinical use. This review outlines the composition, biogenesis, isolation and characterisation methods along with biological and clinical applications of exosomes. Further, the biopharmaceutical features of exosomes include loading method, modified exosomes and potential use of exosomes for different diseases are well explained with the current case studies. We well elaborate the future directions for clinical use of exosomes as drug delivery platforms.

Design and evaluation of microemulsion gel system of nadifloxacin.

Topical microemulsion systems for the antiacne agent, nadifloxacin were designed and developed to overcome the problems associated with the cutaneous delivery due to poor water solubility. The solubility of nadifloxacin in oils, surfactants and cosurfactants was evaluated to screen the components of the microemulsion. Various surfactants and cosurfactants were screened for their ability to emulsify the selected oily phase. The pseudoternary diagrams were constructed to identify the area of microemulsion existence. The influence of k(m) (surfactant/cosurfactant) ratio on the microemulsion existence region was determined and optimum systems were designed. The systems were assessed for drug-loading efficiency and characterised for optical birefringence, pH and refractive index, robustness to dilution, globule size, drug content and thermodynamic stability. Optimised microemulsion systems were formulated into gel form and evaluated for viscosity, spreadability, drug content, ex vivo skin permeation and antibacterial activity. The maximum solubility of nadifloxacin in the microemulsion system was found to be 0.25%. The nadifloxacin microemulsions had a small and uniform globule size (67.3-121.23 nm). The stability results revealed that all formulations showed a stable globule size and the polydispersity index under stress conditions. Incorporation of nadifloxacin in microemulsion gel increased the ex vivo skin permeation and antibacterial activity when compared to marketed cream.