Drug Delivery Letters - Volume 7, Issue 3, 2017

Background and Objective: Around 70% of the pipeline drugs and 40% of marketed drugs come under the BCS class of II and IV. Dissolution of these drugs is a major concern for formulation scientists as poorly soluble drugs consequently affects the bioavailavbility, thus reducing the therapeautic efficacy of these drugs. Discussion: This has led to the development of various new technologies like solid dispersions, micro and nanoparticles of various natural, semi-synthetic and synthetic polymers, among others, of which, the more efficacious lipid based delivery systems have gained wider attention, chiefly due to their lipophilicity and at the same time be safe and economic for commercialisation. But a major hurdle in this regard is the unavailability of proper guidelines regarding characterisation of the lipid based formulations. Majority of the cases, the in vitro characterisation data could not be correlated with that of in-vivo data owing to several physiological factors like lipase, co-lipase, bile salts, pH, etc. Normal dissolution methods are unable to assess the different transformation in the lipid systems in presence of in-vivo conditions affect the drug release rate and thereby the bioavailability. Conclusion: This review covers in vitro lipolysis studies, their working principles, various developments and associated analytical techniques. This review will also focus on how in vitro lipolysis studies play a major role in characterising as developing an in vitro in-vivo correlation (IVIVC) for lipid based formulations.

Background and Objective: Microemulsions (MEs) are thermodynamic stable dispersion of oily phase and aqueous phase stabilized by surfactants, and frequently, with a combination of additives or co-surfactants. Discussion: This system may be either oil dispersed in water (O/W) or water dispersed in oil (W/O). MEs are characteristically transparent solutions, as the globule size is about 100 nanometers or less. MEs are impressive and prospective drug delivery systems due to their thermodynamic stability, enhanced drug solubilisation, and effortlessness of development and administration. A proliferation of in vitro and in vivo studies confirmed that drugs integrated into ME systems providing sustained release and higher bioavailability. The enhancing bioavailability of the systems materializes due to a diversity of factors depending on the components and the ensuing nanostructure. Conclusion: This review is an effort to summarize the current development in the area of MEs, self microemulsifying drug delivery system (SMEDDS) which are examined in relation to their application in different route of administrations like ocular, parentral, and topical. The noteworthy patent, in vitro and in vivo correlation related with these ME systems are also explored here.

Background and Objective: One of the most important obstacles for effective management of diabetics using oral hypoglycaemic agents is because of poor solubility of these agents in aqueous medium. In last few decades, varieties of approaches have been investigated to enhance the solubility and bioavailability of poorly soluble antidiabetic agents. Discussion: This review article highlights the important aspects of nanotechnological based approaches such as polymeric nanoparticles, solid lipid particles, micelles liposome, niosome, microemulsion, solid self-micro emulsifying drug delivery system, and different nano-assemblies. Conclusion: Among all these carriers, it has been proved that the polymeric nanocarrier is an outstanding approach approach for maintaining normoglycaemia for prolonged period of time without the occurrence of side effects. This article aims to provide the current status, analysis of various nano technological based approaches with potential advantages and drawbacks, which helps to identify future directions.

Background and Objective: Lipid based nanoformulations have attracted a lot of attention in recent market because of their nano size properties, high degree of biocompatibility and versatility. Various lipid based formulation are available in market like liposomes, niosomes, solid lipid nanoparticles, nano structured lipid carrier for oral, topical, pulmonary or parenteral route based on disease conditions. Discussion: Whenever lipid based formulation is developed then there is a necessity to check its oral bioavailability in human which is very time consuming process and cost of process is also increases. IVIVC is great tool for such a lipid based nanoformulations. IVIVC predictive mathematical model describes the relationship between an in-vitro property of a dosage form and it's in-vivo response. IVIVC can be used in the development of new pharmaceuticals to reduce the number of human studies during the formulation development and ultimately it decreases time which spent during in-vivo study. Conclusion: Thus, the main objective of an IVIVC is to serve as a surrogate for in-vivo bioavailability study and also support biowaivers. This article provides the information about levels of IVIVC, purpose of IVIVC, factors affecting IVIVC, various steps involved in IVIVC development, IVIVC study in lipid based formulation.

Background and Objective: Gastroretentive dosage forms have emerged as efficient means for oral controlled delivery of several drugs. The objective of this review is to bring under one umbrella, all the necessary knowledge regarding gastroretentive dosage forms, especially floating dosage forms. Methods: The review covers basic anatomy and physiology of gastrointestinal tract, gastric emptying and related problems in drug absorption, candidate drugs and drugs unsuited for gastroretentive formulations, pharmacokinetics of gastroretentive formulations and factors affecting gastric residence time of dosage forms. Various approaches coined by different researchers to achieve prolonged gastric residence time like low density floating systems, high density sinking systems, modified shape systems, size controlled systems, muco-adhesive systems and magnetic systems are also detailed. Special emphasize is given to floating dosage forms, their advantages, disadvantages, excipients used in the formulation, critical parameters and methods of evaluation. Conclusion: The article is expected to motivate the researchers to investigate on gastroretentive dosage forms systematically.

Background and Objective: Single-unit solid oral dosage forms such as tablets and capsules are considered the most common and acceptable form of immediate release systemic drug delivery systems. On the other hand, multiple-unit pellet systems (MUPS) have in recent years become an important dosage form that offers various advantages over conventional single-unit solid oral dosage forms. Discussion: These advantages include, amongst others, reduced risk of local irritation and toxicity, more predictable bioavailability, reduced likelihood of dose dumping and minimised fluctuations in the plasma concentration of the drug. MUPS comprise of relatively small uncoated or coated spherical particles (pellets or beads) compressed into tablets (MUPS tablets) or filled into hard gelatine capsules (MUPS capsules). Conclusion: Application of MUPS technology has led to the successful formulation of various marketed products such as omeprazole in Losec® MUPS tablets, which has resulted in increased drug bioavailability and improved pharmacological response. Another application of MUPS technology is controlled drug release, for example theophylline MUPS capsules (Elixophyline®), which offer sustained drug release.

Aim and Objective: Aim of this study was to evaluate the skin penetration performance of water insoluble glycyrrhetinic acid (GHA) nanocrystals in comparison to the gel and o/w nanoemulsion formulation of water soluble glycyrrhizic acid salt (GA). Methods: The GHA-SmartCrystal® was prepared using bead milling followed by high pressure homogenization. The nanocrystals and o/w nanoemulsion were prepared by homogenization. All formulations were tested for their in vitro penetration and in vivo permeation performance. Results and Discussion: The SmartCrystal® and o/w nanoemulsion had mean particle size of 158 nm and 183 nm, respectively. The zeta potential values of both the formulations were about -30 mV which indicated a good physical stability. After 24 h, the cumulative in vitro skin penetration was 3.29 μg/cm2, 7.13 μg/cm2, 4.24 μg/cm2 and 3.64 μg/cm2 or GHA-coarse suspension, GHA SmartCrystal®, o/w nanoemulsion and GA-gel, respectively in pig ear skin. The cumulative amount of active recovered from the tapes was 4.52 μg/cm2, 93.24 μg/cm2, 9.64 μg/cm2 and 5.55 μg/cm2 for GHA coarse suspension, SmartCrystal®, GA-o/w nanoemulsion and GA-gel, respectively suggesting superior performance of developed nanocrystals. Conclusion: SmartCrystals and nanocrystals showed higher cumulative drug penetration when tested in vitro and in vivo. SmartCrytals offered superior performance of GHA due to smaller particle size and enhanced penetration property. SmartCrytals can be easily mixed with any topical or dermal dosage carriers like gel, cream or lotion for ease of application.

Background: Poor pharmacokinetic profile, bioavailability, solubility and toxicity to healthy tissues hamper clinical application. Encapsulation of gedunin from the neem plant possessing anticancer potential, in chitosan nanoparticles, may overcome these issues and increase antiproliferative property. Methods: Chitosan nanoparticles were prepared by an ionic gelation method. Cells were exposed to gedunin (1.5625 - 50 μg/mL) and the nanoformulation (0.469 - 15 μg/mL) for 24, 48 and 72 h, with paclitaxel as the positive control. Their inhibitory activities were investigated by Sulphorhodamine B assay, coupled with microscopic visualization through a phase-contrast microscope. Results: Encapsulation efficiency of gedunin in chitosan was 98 %, with average particle size of 163.2 ± 24.28, and a zeta potential of +24.2 ± 3.75. Dose- and time-dependent cytomorphological changes resulting in cell death were observed. Nano-gedunin demonstrated much higher antiproliferative activities against NCI-H292 cells at significant levels (p < 0.05). The mean IC50 values for gedunin were approximately 26, 23, and 20 μg/mL at 24, 48, and 72 h, respectively. In contrast, chitosan- encapsulated gedunin recorded a 3 to 8-fold decrease (7.5, 5, and 2 μg/mL). Conclusion: The chitosan nano-delivery system enhanced the cytotoxic activity of gedunin in vitro against NCI-H292 cells and reduced cytotoxicity towards normal lung fibroblast cells (MRC-5).