Arun Nanda

Current Developments Using Emerging Transdermal Technologies In Physical Enhancement Methods.

Transdermal drug delivery using patches offers many advantages, but is limited primarily by the stratum corneum barrier. Amongst the various methods to overcome this barrier, physical methods are gaining in popularity and commercial devices development. Macroflux, MTS and Silex are based on microporation, involving use of microneedles that pierce thereby bypassing the stratum corneum. Intraject , Powderject and Helios are based on needleless jet injectors wherein very fine, solid particulate drug, is fired directly into the skin, using high-pressure gas. Med- Tats incorporate use of modified drug-containing tattoos, which bind to the skin, wherein the drug is absorbed. CHADD is based on use of heat, which increases skin - permeation of drugs. High-power, pulsed lasers transmit positive mechanical forces to the skin and create intercellular channels into the skin transiently. Sonophoresis involves use of ultrasound, which transiently disrupts the stratum corneum barrier. This technique offers a non-invasive transdermal extraction of interstitial fluids of sampling body fluids. Modified Liposomes include Ethosomes (containing alcohol) and Transferosomes (containing surfactants), which have enhanced skin permeability. Pulsed magnetic fields may create transient pores in cell membranes, including skin, resulting in increased permeation. Iontophoresis is based on application of electric potential for enhancing the movement of substances to and from the body. Dupel, Ionzyme, Liposite, ETrans, Phoresor and Drionic are based on iontophoresis. GlucoWatch offers non-invasive blood glucose monitoring, based on reverse iontophoresis. This review outlines recent commercial developments in physical transdermal drug delivery technology and the specific devices and applications being targeted by the pharmaceutical industry.

Optimization and evaluation of gastroretentive ranitidine HCl microspheres by using design expert software

The current study involves the development and optimization of their drug entrapment and ex vivo bioadhesion of multiunit chitosan based floating system containing Ranitidine HCl by ionotropic gelation method for gastroretentive delivery. Chitosan being cationic, non-toxic, biocompatible, biodegradable and bioadhesive is frequently used as a material for drug delivery systems and used to transport a drug to an acidic environment where it enhances the transport of polar drugs across epithelial surfaces. The effect of various process variables like drug polymer ratio, concentration of sodium tripolyphosphate and stirring speed on various physiochemical properties like drug entrapment efficiency, particle size and bioadhesion was optimized using central composite design and analyzed using response surface methodology. The observed responses were coincided well with the predicted values given by the optimization technique. The optimized microspheres showed drug entrapment efficiency of 74.73%, particle size 707.26 μm and bioadhesion 71.68% in simulated gastric fluid (pH 1.2) after 8 h with floating lag time 40s. The average size of all the dried microspheres ranged from 608.24 to 720.80 μm. The drug entrapment efficiency of microspheres ranged from 41.67% to 87.58% and bioadhesion ranged from 62% to 86%. Accelerated stability study was performed on optimized formulation as per ICH guidelines and no significant change was found in drug content on storage.

In vitro antimicrobial activity of methanolic leaf extract of Psidium guajava L.

Aim: This study was designed to examine the chemical composition and in vitro antimicrobial potential of methanolic extract of Psidium guajava Linn (Myrtaceae). Materials and Methods: The inhibitory effect of methanolic extract of P. guajava was tested against three bacterial and two fungal strains by using the paper disc diffusion method. Results: The methanolic extract exhibited antibacterial activity against E. coli with minimum inhibitory concentration, 0.78 μg/ml, minimum bactericidal concentration of 50 μg/ml, and appreciable antifungal activity with minimum inhibitory concentration of 12.5 μg/ml. Preliminary phytochemical analysis of methanolic extract revealed the presence of antimicrobial compounds such as flavonoids, steroids, and tannins, which may contribute for the antimicrobial action of P. guajava. Conclusion: The extract was found to be bacteriostatic and fungistatic in action.

A comparative evaluation of price and quality of some branded versus branded-generic medicines of the same manufacturer in India

Objective: To compare and evaluate the price and quality of “branded” and branded-generic equivalents of some commonly used medicines manufactured by the same pharmaceutical company in India. Materials and Methods: Five commonly used medicines: alprazolam, cetirizine, ciprofloxacin, fluoxetine, and lansoprazole manufactured in branded and branded-generic versions by the same company were selected. Price-to-patient and price-to-retailers were found for five “pair” of medicines. Both quantitative and qualitative analysis were performed following the methods prescribed in the Indian Pharmacopoeia 2007 on five pair of medicines. The tests performed were identification test, chemical composition estimation test, uniformity of contents test, uniformity of weight, and dissolution studies. Main Outcome Measures: Price-to-patient, retailer mark-up and qualitative analysis of branded and branded-generic medicines. Results: Retailer margin for five branded medicines were in the range of 25-30% but for their branded-generics version manufactured by the same company it was in the range of 201-1016%. Price-to-patient for the branded version of cetirizine, fluoxetine, ciprofloxacin, lansoprazole, and alprozolam was higher by 41%, 33%, 0%, 14%, and 31% than branded-generic. Both versions of five medicines were within their permissible range for all the quantitative and qualitative parameters as prescribed in Indian Pharmacopoeia. Conclusion: Difference in price-to-patient was not as huge as it is expected for generics but margins for retailer were very high for branded-generics. Quality of branded-generics is same as for their branded version. The study highlights the need to modify the drug price policy, regulate the mark-ups in generic supply chain, conduct and widely publicize the quality testing of generics for awareness of all stakeholders.

Metal analysis in Citrus Sinensis fruit peel and Psidium Guajava leaf

The determination of metal traces is very important because they are involved in biological cycles and indicate high toxicity. The objective of the present study is to measure the levels of heavy metals and mineral ions in medicinally important plant species, Citrus sinensis and Psidium guajava. This study investigates the accumulation of Copper (Cu), Zinc ( Zn), Cadmium (Cd), Aluminum (Al), Mercury (Hg), Arsenic (As), Selenium (Se) and inorganic minerals like Calcium (Ca) and Magnesium (Mg) in C. sinensis (sweet orange) fruit peel and P. guajava (guava) leaf, to measure the levels of heavy metal contamination. Dried powdered samples of the plants were digested using wet digestion method and elemental determination was done by atomic absorption spectrophotometer. Results are expressed as mean ΁ standard deviation and analysed by student′s ′t′ test. Values are considered significant at P < 0.05. The results were compared with suitable safety standards and the levels of Cu, Zn, Cd, Mg and Ca in C. sinensis fruit peel and P. guajava leaves were within the acceptable limits for human consumption. The order of concentration of elements in both the samples showed the following trend: Mg > Ca > Al > Zn > Cu > Cd > Hg = As = Se. The content of Hg, As and Se in C. sinensis fruit peel and P. guajava leaves was significantly low and below detection limit. The content of toxic metals in tested plant samples was found to be low when compared with the limits prescribed by various authorities (World Health Organization, WHO; International Centre for Materials Research, ICMR; American Public Health Association, APHA). The content of Hg, As and Se in C. sinensis fruit peel and P. guajava leaves was not detectable and met the appropriate safety standards. In conclusion, the tested plant parts taken in the present study were found to be safe.

Nanotechnology in cosmetics: a boon or bane?

Recent advances in the field of nanotechnology enabled the manufacturing of elaborated nanometer-sized particles for various biomedical applications. The cosmetic industry is one of the most enthusiastic early adopters of nanotechnology which routinely uses nano-scale ingredients. However, in the absence of mandatory product labeling, it is difficult to estimate the number of cosmetics, sunscreens and personal care products containing nanoparticles that are now commercially available. The increased capacity of nanoparticles to penetrate skin and gain access to human cells is a double-edged sword as it may be useful for medical purposes, but might also result in far greater uptake of substances that exert adverse health effects. Since nanomaterials represent a large group of structurally, physically, and chemically variable substances, specific toxicological studies are required for each product prior to commercialization. This review aims to delineate the most investigated applications, risk and safety considerations, and regulation of nanotechnology in the field of cosmetics.

In vitro antimicrobial status of methanolic extract of Citrus sinensis Linn. fruit peel

Aim : The present investigation evaluated the antimicrobial potential of methanolic extract of Citrus sinensis Linn. (Rutaceae) fruit peel. There is a basis for the traditional use of this plant for local health remedies. Materials and Methods: The antimicrobial activity of methanolic extract of C. sinensis fruit peel was tested against three bacterial and two fungal strains. Turbidimetric or tube dilution method and paper disc diffusion method were followed. Results are expressed as mean ± standard deviation. Results: The C. sinensis fruit peel methanolic extract exhibited antibacterial activity against Escherichia coli with minimum inhibitory concentration of 0.78 μg/ ml and minimum bactericidal concentration of 6.25 μg/ml, and appreciable antifungal activity with minimum inhibitory concentration of 12.5 μg/ml. The phytochemistry of C. sinensis fruit peel methanolic extract revealed the presence of carbohydrates (reducing sugars, hexose sugars, non-reducing polysaccharides, gums, and mucilages), flavonoid glycosides, coumarin glycosides, volatile oils, organic acids, fats and fixed oils. Conclusion: Most of the organic chemical constituents reported are aromatic phenolic compounds, which are known for their wide spectra of antimicrobial activity. Therefore, the bacteriostatic and fungistatic action of the tested extract may be attributed to the presence of polyphenolic compounds. In short, C. sinensis fruit peel methanolic extract is a potential source of natural antimicrobials.

A comparative study of regulatory trends of pharmaceuticals in Brazil, Russia, India and China (BRIC) countries:

BRIC basically include the emerging markets of Brazil, Russia, India and China. The growth of pharmaceutical market in these countries has been very eye-popping during the last two decades. The growth of pharmaceutical market depends upon the drug regulatory system and drug regulatory laws. The drug regulatory system in these countries is on the way of continuous improvement e.g. introduction of product patent in India, provisions for drug approval in China, bioequivalence testing requirement in Brazil, Russian new law on circulation of medicines 2010. In this article the drug regulatory system of BRIC countries has been analyzed. These drug regulatory trends include following: drug regulatory framework, drug regulatory laws, clinical trials, drug registration procedures, drug pricing mechanism, GMP practices, pharmacovigilance, patents system on pharmaceuticals, patent linkage and data protection, etc. Drug regulatory framework has been analyzed by studying the composition of various central and state drug regulatory authorities and drug testing institutions regulating the pharmaceutical industry. The basic drug regulatory laws regulating approval, manufacturing, packing, labeling, selling, advertising, use of drugs, cosmetics and medical devices has been reported. The drug pricing mechanism over the essential and nonessential drugs and drug price calculation formula has been reported. The drug manufacturing law, manufacturing approval and inspection system has also been analyzed. The pharmacovigilance system for the reporting of Adverse Drug Reactions in these countries has been studied. Finally an analysis of the intellectual property rights related to pharmaceuticals has been made in BRIC countries.

Enhancement of Percutaneous Absorption of Propranolol Hydrochloride by Iontophoresis

AbstractIontophoresis is defined as the migration of ions when an electric current passes through a solution containing ionized species. When applied transdermally, iontophoresis may reduce the barrier porperties of skin and may enhance the transdermal permeation of drugs. This research work was aimed at exploring the factors which influence the effectiveness of iontophoresis facilitated transport of ionized species across the skin, and comparing it with that by passive diffusion. Propranolol hydrochloride was selected as the model drug, and rat abdominal skin as the in-vitro animal model. Pulse dc was applied, at 2.16/3/6/9 mA/cm2; 1:1 or 4:1 duty cycle and 20 KHz frequency for 15/25 minutes. Factors which modify the iontophoretic drug delivery, such as drug concentration, current density, duty-cycle of pulse dc, and duration of iontophoresis, were also evaluated. It was found that iontophoresis causes a significant increase in transdermal permeation of Propranolol hydrochloride in-vitro through rat abdo...

Compulsory licensing of drug products in developing countries

Compulsory licensing of drug products is a very hot issue in today’s pharmaceutical world. Compulsory licensing of a drug product allows the government to issue the license of manufacturing the drug to a third person. The third person has to give some 5–10% royalty to the patent holder (the quantum of royalty is decided by the government and not by the patentee). The issue emerged after developing nations were given TRIPS flexibilities to implement the system when lives of large population are at stake. Compulsory licenses have been given in many countries like Thailand, Brazil, Mozambique, Zimbabwe, Zambia, Rwanda, Malaysia, Indonesia and recently India. India issued compulsory license over Bayer’s anticancer drug Naxaver (Sorafenib) to generic company Natco Pharma Ltd. United States has criticized the Indian decision. United States has also put Thailand on watch list after Thailand has issued compulsory licenses to three antiretroviral drugs. Compulsory licensing of drug products is very beneficial for the patients but is considered a big threat for the pharmaceutical companies. The branded drug makers spend billion dollars to patent a drug product. It is claimed by the pharmaceutical majors that the royalty of 5–10% given by generic drug makers to these companies is not enough to recoup their loss. The present article explores the utilization of “Compulsory Licensing” by several countries, exemplified by India and Brazil in particular, and highlights the patentees’ concerns of losing profits. The authors have attempted to negate the concern of the patentees over the use of compulsory licensing.