Pharmaceutical Nanotechnology - Volume 7, Issue 4, 2019

Most of the active pharmaceutical ingredient used in the management of disease have poor water solubility and offer grueling problems in drug formulation development since low solubility is generally associated with poor dissolution characteristics which leads to poor oral bioavailability. The great challenge for the development of a pharmaceutical product is to create its new formulation and drug delivery system to limit solubility problems of existing drug candidate. Limited drug-loading capacity requires a large amount of carrier material to get appropriate encapsulation of the drug, which is another major challenge in the development of pharmaceutical product which could be resolved by developing nanocrystals (NCs). A significant research in the past few years has been done to develop NCs which helps in the delivery of poorly water soluble drugs via different routes. The technology could continue to thrive as a useful tool in pharmaceutical sciences for the improvement of drug solubility, absorption and bioavailability. Many crystalline compounds have pulled in incredible consideration much of the time, due to their ability to show good physical and chemical properties when contrasted with their amorphous counterparts. Nanocrystals have been proven to show atypical properties compared to the bulk. This review article explores the principles of the important nanocrystallization techniques including NCs characterization and its application.

Nitric oxide (NO) is a short-lived, endogenously produced, signaling molecule which plays multiple roles in mammalian physiology. Underproduction of NO is associated with several pathological processes; hence a broad range of NO donors have emerged as potential therapeutics for cardiovascular and respiratory disorders, wound healing, the immune response to infection, and cancer. However, short half-lives, chemical reactivity, rapid systemic clearance, and cytotoxicity have hindered the clinical development of most low molecular weight NO donors. Hence, for controlled NO delivery, there has been extensive effort to design novel NO-releasing biomaterials for tumor targeting. This review covers the effects of NO in cancer biology, NO releasing moieties which can be used for NO delivery, and current advances in the design of NO releasing biomaterials focusing on their applications for tumor therapy.

Background: Folic acid is essential in many metabolic processes and DNA synthesis. Nevertheless, folic acid is not stable, pH-sensitive, and deteriorated upon light exposure. Objective: This work was aimed to improve folic acid stability within vitamin E-based nanoemulsion. Methods: The nanoemulsion was prepared with self-nanoemulsification method by mixing vitamin E oil, Tween 20, and PEG 400. A pseudoternary phase diagram was constructed with aqueous titration to determine the optimum ratio for the mixture. The globule size, pH and entrapment efficiency were included in the nanoemulsion characterizations. In addition, the influence of centrifugation, storage, and pH on physical and chemical stabilities of folic acid nanoemulsion was evaluated. Results: Optimum formula was obtained from vitamin E, Tween 20, and PEG 400 with the ratio of 1:11:1, and the folic acid amount was 8 mg. The size of folic acidloaded oil globule was 15.10 ± 1.51 nm, and the nanoemulsion pH was 6.24 ± 0.01. The nanoemulsion system was able to load the folic acid completely. Folic acid in nanoemulsion was stable after 14 days at room temperature, and it was more stable compared to folic acid in solution. In addition, the physical and chemical characteristics of folic acid in nanoemulsion was not affected by the simulated gastric condition. Conclusion: Hence, nanoemulsion is a promising strategy to enhance folic acid stability.

Background: Development of polymeric micelles for the management of allergic conjunctivitis to overcome the limitations of topical installation, such as poor patient compliance, poor stromal permeability, and significant adverse effects, increase precorneal residence time and efficacy, and also control the release of drug at the target site. Objective: The investigation was aimed at developing a polymeric micellar system of Azelastine HCl for Ocular Delivery. Methods: Drug loaded micelles of tri-block copolymers Pf 127 were prepared by Thin Film hydration method. The polymeric micelles formulations (F1 to F9) were assessed for entrapment efficiency, micelle size, in vitro permeation, ex vivo transcorneal permeation, in vivo Ocular Irritation, and Histology. Results: Optimized micelles formulation (F3), with the lowest micelle size of 92 nm, least polydispersity value of 0.135, highest entrapment efficiency of 95.30 ± 0.17%, and a cumulative drug permeation of 84.12 ± 1.26% in 8h, was selected to develop pH-sensitive micelles loaded carbopol in situ gel. The optimized in situ gel (G4) proved to be superior in its ex vivo transcorneal permeation when compared with Market Preparation and pure drug suspension, exhibiting 43.35 ± 1.48% Permeation with zero-order kinetics (r2 = 0.9944) across goat cornea. Transmission Electron microscopy revealed spherical polymeric micelles trapped in the gel matrix. A series of experiments showed hydration capability, non-irritancy, and histologically safe gel formulation that had appropriate handling characteristics. Conclusion: A controlled release pH-sensitive ocular formulation capable of carrying the drug to the anterior section of the eye via topical delivery was successfully developed for the treatment of allergic conjunctivitis.

Background: Phosal based excipients are liquid concentrates containing phospholipids. They are used to solubilize water-insoluble drug and also act as an emulsifier to get the smallest droplet size of the formed emulsion after administration. Objective: The aim is to prepare phosal based self nanoemulsifying drug delivery system (SNEDDS) for water insoluble drug zaltoprofen. Methods: The various parameters like solubility of drug in different vehicles, ternary phase diagram are considered to formulate the stable emulsion which is further characterized by Self emulsification time and globule size analysis to optimize liquid SNEDDS of Zaltoprofen. Optimized L-SNEDDS was converted into free-flowing powder Solid-SNEDDS (S-SNEDDS). S-SNEDDS was evaluated for Globule size analysis after reconstitution, in vitro dissolution study and in vivo pharmacokinetic study in rats. Results: Phosal 53 MCT with highest drug solubility was used as oil along with Tween 80 and PEG 400 as surfactant and cosurfactant respectively to prepare liquid SNEDDS. Neusilin us2 was used as an adsorbent to get free-flowing S-SNEDDS. S-SNEDDS showed improved dissolution profile of the drug as compared to pure drug. In vivo study demonstrated that there is a significant increase in Cmax and AUC of S-SNEDDS compared to zaltoprofen powder. Conclusion: Phosal based SNEDDS formation can be successfully used to improve the dissolution and oral bioavailability of poorly soluble drug zaltoprofen.