Varun Garg

ETHOSOMES AND TRANSFERSOMES: PRINCIPLES, PERSPECTIVES AND PRACTICES.

BACKGROUND The success story of liposomes in the treatment of systemic infectious diseases and various carcinomas lead the scientists to the innovation of elastic vesicles to achieve similar success through transdermal route. In this direction, ethosomes and transfersomes were developed with the objective to design the vesicles that could pass through the skin. However, there is a lack of systematic review outlining the principles, method of preparation, latest advancement and applications of ethosomes and transfersomes. This review covers various aspects that would be helpful to scientists in understanding advantages of these vesicular systems and designing a unique nano vesicular delivery system. METHODS Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was culminated in terms of principle of these vesicular delivery systems, composition, mechanism of actions, preparation techniques, methods for their characterization and their application. RESULTS A total of 182 papers including both, research and review articles, were included in this review in order to make the article comprehensive and readily understandable. The mechanism of action and composition of ethosomes and transfersomes was extensively discussed. Various methods of preparation such as, rotary film evaporation method, reverse phase evaporation method, vortex/ sonication method, ethanol injection method, freeze thaw methods, along with their advantages has been discussed. It was also discussed that both these elastic nanocarriers offer unique advantages of ferrying the drug across membranes, sustaining drug release as well as protecting the encapsulated bio actives from external environment. The enhanced bioavailability and skin penetration of ethosomes as compared to conventional vesicular delivery systems is attributed to the presence of ethanol in the bilayers while that for transfersomes accrues due to their elasticity along with their ability to retain their shape because of the presence of edge activators. Successful delivery of synthetic drugs as well as phytomedicines has been extensively reported through these vesicles. CONCLUSION Though these vesicular systems offer a good potential for rational drug delivery, a thoughtfully designed process is required to optimize the process variables involved. Industrial scale production of efficacious, safe, cost effective and stable formulations of both these delivery systems appears to be a pre-requisite to ensure their utility as the trans-dermal vehicles.

Oral Delivery of Antidiabetic Polypeptide-k: Journey so far and the Road Ahead.

The prevalence of diabetes mellitus is growing rapidly. According to the global report of International Diabetes Fedration (IDF), about 382 million people are suffering from diabetes and among them, 90% cases were of type-II. By 2035, it is expected that this number will reach to 592 million. In the last 5 decades, various efforts have been put towards the development of synthetic medicines or synergistic combination of herbal and synthetic medicines to treat diabetes mellitus. Polypeptide-k is an antihyperglycaemic protein isolated from dried seeds collected from ripened fruits of Momordica charantia. Extensive research has been carried out in the last fifteen years on polypeptide-k to explore its potential applications for the treatment of both types of diabetes mellitus. This review highlights the available marketed formulations and research investigations conducted on humans to prove the potential of polypeptide-k as an antihyperglycaemic agent. This article also marks the reasons and need for oral delivery of polypeptide-k.

Nanosuspension: Principles, Perspectives and Practices

In the last three decades, nano-sizing of hydrophobic drugs has emerged as one of the most commonly used strategies to overcome their solubility and bioavailability related issues. Nanosuspensions offer versatile features and unique advantages over other approaches that have been utilized for this purpose. The unique inherent properties of nanosuspensions have been explored for a wide variety of applications. Commercial production of stable nanosuspensions has been made possible by the use of techniques such as media milling and high pressure homogenization. This article reviews various techniques being employed for production, characterization, merits and limitations of nanosuspensions and mechanisms that play a role in the physicochemical stability of nanosuspensions. The common strategies applied so far to overcome their stability and commercialization related aspects are also highlighted.

Solid self-nanoemulsifying drug delivery systems for oral delivery of polypeptide-k: Formulation, optimization, in-vitro and in-vivo antidiabetic evaluation

&NA; Development of self‐nanoemulsifying drug delivery systems (SNEDDS) of polypeptide‐k (PPK) is reported with the aim to achieve its oral delivery. Box‐Behnken design (BBD) was adopted to develop and optimize the composition of SNEDDS. Oleoyl polyoxyl‐6 glycerides (A), Tween 80 (B), and diethylene glycol monoethyl ether (C) were used as oil, surfactant and co‐surfactant, respectively as independent variables. The effect of variation in their composition was observed on the mean droplet size (y1), polydispersity index (PDI) (y2), % drug loading (y3) and zeta potential (y4). As per the optimal design, seventeen SNEDDS prototypes were prepared. The optimized composition of SNEDDS formulation was 25% v/v Oleoyl polyoxyl‐6 glycerides, 37% v/v Tween 80, 38% v/v diethylene glycol monoethyl ether, and 3% w/v PPK. The optimized formulation revealed values of y1, y2, y3, and y4 as 31.89 nm, 0.16, 73.15%, and −15.65 mV, respectively. Further the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, disintegration and dissolution properties. Both, liquid and solid‐SNEDDS have shown release of >90% within 10 min. The formulation was found stable with change in pH, dilution, temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline PPK was observed in amorphous state in solid SNEDDS when characterized through DSC and PXRD studies. The biochemical, hematological and histopathological results of streptozotocin induced diabetic rats shown promising antidiabetic potential of PPK loaded in SNEDDS at its both the doses (i.e. 400 mg/kg and 800 mg/kg) as compared to its naïve form at both the doses. The study revealed successful formulation of SNEDDS for oral delivery of PPK. Graphical abstract Figure. No caption available.

A Novel Three-pronged Approach for Colon Delivery of Sulfasalazine: Concomitant Use of pH- Responsive, Microbially Triggered Polymers and Liquisolid Technology

OBJECTIVE A major challenge in targeting orally administered drugs to colon is their passage through the long gastrointestinal path comprising highly variant conditions in terms of pH, viscosity, gut motility and microbial flora. Approaches to pH controlled release and microbially triggered release have proved to be successful in achieving colon targeting only to a partial extent. METHODS In an attempt to improve targeting, both these approaches have been combined together with the approach of liquisolid technology which, hitherto, remains unexplored for colon targeting. The combination of these three approaches is being reported for the first time to achieve colon targeting along with a burst release of a Biopharmaceutical Classification System (BCS) Class IV drug at the target site. pH controlled polymer, Eudragit® S-100 was used to prevent the release of sulfasalazine in the gastric region while microbially triggered polymers, pectin and guar gum were used to ferry the system through the intestinal region. RESULTS Liquisolid formulation was designed to provide a burst release of sulfasalazine in colon on the digestion of polysaccharide coating. CONCLUSION The results support the premise that the combination of pH sensitive, microbially triggered polymers and liquisolid formulation technique appears to be a pragmatic approach for colonic delivery of orally administered drugs.

Novel biorelevant dissolution medium as a prognostic tool for polysaccharide-based colon-targeted drug delivery system

To overcome the limitations of the conventionally used methods for evaluation of orally administered colon-targeted delivery systems, a novel dissolution method using probiotics has been recently reported. In the present study, universal suitability of this medium composed of five different probiotics is established. Different delivery systems – mini tablets, liquisolid compacts, and microspheres coated with different polysaccharides – were prepared and subjected to sequential dissolution testing in medium with and without microbiota. The results obtained from fluid thioglycollate medium (FTM)-based probiotic medium for all the polysaccharide-based formulations showed statistically similar dissolution profile to that in the rat and goat cecal content media. Hence, it can be concluded that the developed FTM-based probiotic medium, once established, may eliminate the need for further animal sacrifice in the dissolution testing of polysaccharide-based colon-targeted delivery system.

Application of self-emulsifying delivery systems for effective delivery of nutraceuticals

Abstract Poor bioavailability is one of the major limitations in absorption of certain nutraceuticals after their oral intake. This is especially applicable to vitamins, phytoconstituents, enzymes, and certain antioxidants. A number of formulation strategies are being developed for overcoming the problems related to oral absorption and bioavailability of these nutraceuticals. Lipid-based formulations are one of the attractive choices for enhancing oral bioavailability. One such novel system that has been successfully explored is the self-emulsifying delivery systems (SEDS). These delivery systems offer advantages like improved solubility and increased bioavailability. SEDS are basically isotropic mixtures of drug, lipids (natural or synthetic oils), and emulsifiers (solid or liquid), usually with one or more of hydrophilic cosolvents/coemulsifiers. A number of SEDS have been developed for vitamins, enzymes, and phytoconstituents that find an application as dietary supplement or as adjuvants in various disease conditions. This chapter not only compiles the available data of various SEDS reported for delivery of nutraceuticals but also describes their future potential after critically viewing their advantages and limitations.