Formulation, optimization, hemocompatibility and pharmacokinetic evaluation of PLGA nanoparticles containing paclitaxel.

OBJECTIVE: Paclitaxel (PTX)-loaded polymer (Poly(lactic-co-glycolic acid), PLGA)-based nanoformulation was developed with the objective of formulating cremophor EL-free nanoformulation intended for intravenous use. SIGNIFICANCE: The polymeric PTX nanoparticles free from the cremophor EL will help in eliminating the shortcomings of the existing delivery system as cremophor EL causes serious allergic reactions to the subjects after intravenous use. METHODS AND RESULTS: Paclitaxel-loaded nanoparticles were formulated by nanoprecipitation method. The diminutive nanoparticles (143.2 nm) with uniform size throughout (polydispersity index, 0.115) and high entrapment efficiency (95.34%) were obtained by employing the Box-Behnken design for the optimization of the formulation with the aid of desirability approach-based numerical optimization technique. Optimized levels for each factor viz. polymer concentration (X1), amount of organic solvent (X2), and surfactant concentration (X3) were 0.23%, 5 ml %, and 1.13%, respectively. The results of the hemocompatibility studies confirmed the safety of PLGA-based nanoparticles for intravenous administration. Pharmacokinetic evaluations confirmed the longer retention of PTX in systemic circulation. CONCLUSION: In a nutshell, the developed polymeric nanoparticle formulation of PTX precludes the inadequacy of existing PTX formulation and can be considered as superior alternative carrier system of the same.

Nutriose, a Dextrin-based Natural Polysaccharide Polymer with Beneficial Activities as a Candidate for Future Drug Delivery: A Review.

Nutriose is a dextrin-based soluble fiber prepared from starch. Cereals such as maize, wheat, and barley are the primary sources of nutrients for commercial production. Nutriose is resistant to digestion by human enzymes in the stomach and small intestine. It is mostly undamaged when it enters the colon after traveling through the digestive tract, where it generates shortchain fatty acids (SCFAs) as byproducts. These SCFAs, which include butyrate, propionate, and acetate, have a number of health advantages. They foster an environment in the colon that is advantageous for gut health-promoting bacteria like lactobacilli and bifidobacteria. Nutriose fermentation leads to a more balanced composition of the gut microbiota, which may have advantages for the immune system, better digestion, and increased nutrient absorption. As a result, nutriose is currently being utilized as a prebiotic. Several publications have previously demonstrated the impact of nutriose on stimulating gut mucosal immunity and boosting colonic fermentation and excretion in rats. Nanoformulations and nutrisomes have already been prepared and evaluated in recent years. A novel nutriose-based polymeric coating mix has already been tested as a potential colon-targeting material. As a natural polysaccharide, nutriose's possible uses in pharmaceuticals may increase in the near future. The purpose of this study is to critically analyze existing data to determine the potential of nutriose as a natural polymer for various drug delivery systems.

A Mini Review on Characteristics and Analytical Methods of Otilonium Bromide.

Irritable bowel syndrome (IBS) is a world-wide disease prevalently in Western nations. It influences about 15% of the western populace, with a negative effect on the quality of life and furthermore on medical services costs. Anticholinergic antispasmodics are first line of treatment for discomfort or abdominal pain, particularly if unrelieved after alleviation of stoppage or antidiarrheal treatment. Otilonium bromide (OTB) is quaternary ammonium compound with action on distal GI tract as antispasmodic. It is utilized in the treatment of patients influenced by Irritable inside disorder (IBS) because of its particular pharmacokinetic and pharmacodynamic properties. OTB is poorly absorbed systematically was viable in contrast with different medications used for same purpose, for example, pinaverium bromide and mebeverine, with a good tolerability profile. The effects are long lasting, even after stopping the dosage regime for reduction of abdominal pain. In this review, an overview of mechanism of action, pharmacologic action, synthesis and particularly various analytical and bioanalytical methods are discussed. The analytical methods discussed are spectrophotometry including Near Infrared Spectroscopy (NIRS), chromatography and capillary electrophoresis methods are described with the range, limit of detection and quantification. The paper also provides details of scope of further extension of analytical methods. It was found that most of the analytical methods involves usage of toxic solvents e.g., methanol, acetonitrile, chloroform etc. posing risk to the analyst as well as environment.

Current Updates in Transdermal Therapeutic Systems and Their Role in Neurological Disorders.

The transdermal therapeutic system plays an important role in the treatment of neuropathic pain. Transdermal drug delivery is considered an ideal therapeutic approach for the management of chronic neurological disorders in the elderly population. It is a simple to use, non-invasive and painless drug delivery system, which provides sustained therapeutic plasma levels of drug for an extended period. Moreover, it bypasses the first-pass metabolism of the active agent, improves bioavailability and reduces undesired adverse effects, which in turn improves patient compliance. Several transdermal delivery systems are currently under investigation for the treatment of Parkinson's syndrome, Alzheimer's disorders, and Neurological pain. Drug delivery via the transdermal route is proposed as an alternative remedy to overcome the drawbacks associated with the conventional dosage forms for chronic neurological disorders. The management of Alzheimer's disease via transdermal drug administration exhibits the greatest therapeutic improvements in the treatment of cognition and global functioning among neuropathic patients. Technological breakthroughs in transdermal drug administration such as the microreservior system, microneedles, metered-dose transdermal spray (MDTS), needle-free injections, and ultrasound-based transdermal therapeutic systems have been successfully used to treat neurological disorders. For example, microneedle (MN) is a highly efficient and versatile device due to its distinctive properties. Ultrasounds have been very popular for the delivery of bioactive agents across the skin barrier. This review focuses on the recent advances of various technologies employed in the transdermal therapeutic systems and their applications on neurological disorders for achieving therapeutic outcomes on patients.

Status of fatty acids as skin penetration enhancers-a review.

Novel techniques for drug delivery have been investigated in human medicine in recent years. The transdermal route of drug delivery has attracted researchers due to many biomedical advantages associated with it. However, excellent impervious nature of skin is the greatest challenge that has to be overcome for successfully delivering drug molecules to the systemic circulation by this route. One long-standing approach for improving transdermal drug delivery uses penetration enhancers (also called sorption promoters or accelerants) that can reversibly compromise the skin's barrier function and consequently allow the entry of otherwise poorly penetrating molecules into the membrane and through to the systemic circulation. A large number of fatty acids have been used as permeation enhancers. They have proven to be effective and safe sorption promoters. This present review includes the classification, feasibility and application of fatty acids as sorption promoters for improved delivery of drug through skin.

Design, development, physicochemical, in vitro and in vivo evaluation of monolithic matrix type transdermal patches containing nitrendipine.

The matrix type transdermal drug delivery systems (patches) of Nitrendipine were prepared by film casting technique. The patches were characterized for physical, in vitro release studies and ex-vivo permeation studies (human cadaver skin). On the basis of in vitro drug release and skin permeation performance, formulation B3 was found to be better than the other formulations and it was selected as the optimized formulation. The final optimized formulation (B3) was subjected to skin irritation, pharmacokinetic, pharmacodynamic and stability studies. The maximum percentage drug release in 48 hours was 94.67 +/- 3.25 for B3 and 91.43 +/- 2.106 for A2 formulation. Again formulation B3 (0.0627 mg/cm2/h) and A2 (0.0566 mg/cm2/h) showed maximum skin flux in the respective series. Patches prepared with Plasdone S-630 were more flexible as compared to PVP K 30 containing patches. Patches prepared with PVP K 30 showed drug release and skin permeation at higher percentage as compared to those containing Plasdone S-630. The interaction studies carried out by comparing the results of ultraviolet, infrared, TLC and DSC analyses for the pure drug, medicated and placebo formulations indicated no chemical interaction between the drug and excipients. The TDDS was found to be free of any skin irritation as suggested by skin irritation score of 1.16 (< 2.00) under Draize score test.

Indian aspects of drug information resources and impact of drug information centre on community.

Drug information centre refer to facility specially set aside for, and specializing in the provision of drug information and related issues. The purpose of drug information center is to provide authentic individualized, accurate, relevant and unbiased drug information to the consumers and healthcare professionals regarding medication related inquiries to the nation for health care and drug safety aspects by answering their call regarding the all critical problems on drug information, their uses and their side effects. Apart from that the center also provides in-depth, impartial source of crucial drug information to meet the needs of the practicing physicians, pharmacists and other health care professionals to safeguard the health, financial and legal interests of the patient and to broaden the pharmacist role visible in the society and community. The service should include collecting, reviewing, evaluating, indexing and distributing information on drugs to health workers. Drug and poisons information centers are best established within major teaching hospitals. This allows access to clinical experience, libraries, research facilities and educational activities. Information present in the current paper will not only enlighten the role of drug information center but also focused on the rational use of drug.

In vitro and in vivo assessment of matrix type transdermal therapeutic system of labetalol hydrochloride.

OBJECTIVE: The aim of the investigation was to develop and evaluate matrix type transdermal therapeutic systems containing new polymeric combinations (Eudragit E PO/Eudragit RL 100 & Plasdone S 630) as polymers and Labetalol Hydrochloride (LBHCl) as a model drug. EXPERIMENTAL: The matrix type TTS of LBHCl were prepared by film casting technique. The patches were characterized for physical, in vitro release studies & ex-vivo permeation studies (human cadaver skin). On the basis of in vitro drug release and skin permeation performance, formulation A1 was found to be better than the other formulations and it was selected as the optimized formulation. The optimized patch was assessed for its pharmacokinetic, pharmacodynamic, skin irritation potential, and stability studies. RESULTS: The maximum percentage drug release & Permeation in 48 hrs were 92.43 % and 76.24 % respectively for optimized patch. The Korsmeyer peppas release exponent value of 0.604 suggested release mechanism towards first order release in the optimized formulation. The results obtained from the in vivo characterization of the optimized patch showed sustained action of the developed formulation. The interaction studies analysis indicated no chemical interaction between the drug and polymers. The optimized patch was seemingly free of potentially hazardous skin irritation as suggested by skin irritation score of 0.915<2.00 (under Draize score test). The optimized formulation was found to be stable at ambient storage conditions. CONCLUSION: The above TTS holds promise for improved bioavailability and better management of hypertension on long term basis.

Formulation and evaluation of monolithic matrix polymer films for transdermal delivery of nitrendipine.

The objective of the present work was to develop a suitable transdermal drug delivery system for nitrendipine. Polymeric films of nitrendipine were prepared by the film casting technique (glass ring) on mercury substrate. They were evaluated for physicochemical parameters, in vitro release and ex vivo permeation (heat separated human epidermis). Release of the drug from the films followed anomalous transport (0.5 < n < 1).Polymeric combination containing Eudragit RL 100:PVP K 30 in a 4:6 ratio showed the best results. Maximum drug release and skin permeability coefficient in 48 h were 85.8% and 0.0142 cm h(-1), respectively, in formulation C3 (Eudragit RL 100/Plasdone S 630; 4:6) and 88.0% and 0.0155 cm h(-1), respectively, in formulation, D3 (Eudragit RL 100/PVP K 30; 4:6). FTIR and TLC studies indicated no drug and polymer interaction.

The effect of penetration enhancers on permeation kinetics of nitrendipine in two different skin models.

The purpose of this research was to evaluate the effect of penetration enhancers on permeation kinetics of nitrendipine (NTP) through two different skin models. The permeation profile and related kinetics parameters such as activity parameter, diffusion parameter, lag time, relative activity parameter and relative diffusion parameter of NTP was determined in presence of some novel and widely accepted permeation enhancers. Among all the more pronounced enhancing effect was obtained with oleic acid (OA) as it presented the highest permeability coefficient. The enhancement was found to be increased in the following order: Dimethyl sulphoxide (DMSO)