Pharmaceutical science

In a number of recent guidance documents, the FDA has placed more emphasis on the meaningful comparison of dissolution profile data. For example, the FDA scale-up and post-approval changes–modified release (SUPAC–MR) guidance indicates that similar dissolution profiles for approved and modified formulations is acceptable justification for certain levels of change without prior FDA approval or the need to perform bioequivalence studies. As a result, interest among pharmaceutical scientists has focused on the methodology that is available for the comparison of dissolution profile data. The authors review the literature on the methods that are currently available.

Hydrogels are one of the upcoming classes of polymer-based controlledrelease drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogels also show stimuli-responsive changes in their structural network and hence, the drug release. Because of large variations in physiological pH at various body sites in normal as well as pathological conditions, pH-responsive polymeric networks have been extensively studied. This review highlights the use of hydrogels (a class of polymeric systems) in controlled drug delivery, and their application in stimuliresponsive, especially pH-responsive, drug release. Bioinformatics: the role and limitations of patents by Teresa J. Welch

The quality system of any modern pharmaceutical company is the pharmaceutical quality system (PQS), which extends the GMP standards to all stages of the medicinal productslife cycle, from pharmaceutical development to its withdrawal from production. The principal difference between PQS and GxP rules from other quality systems is that the medicinal product, its safety and efficacy is put at the forefront. At the same time, PQS implies a process approach to all components that should be aimed at achieving the main goal-ensuring and guaranteeing the quality of the medicinal product for the end user (patient)-and should be based on the quality risk management system. An integral part of PQS, as well as the GxP rules adopted in the European Union and PIC/S, is a process for self-inspections and/or quality audits, which regularly appraises the effectiveness and applicability of the PQS. This publication is dedicated to the definition of self-inspections (internal audits) as one of the PQS's processes. The article defines the main standard stages and develops a model of a risk-based approach to the self-inspections' planning in relation to processes of the pharmaceutical quality system.

Background: The present review article provides an overview of the published literature concerning microbial quality of medicinal plants and products and their decon-tamination methods. It is important to analyze different aspects regarding the cultivation, growing, harvesting, storage, manufacturing, and decontamination of medicinal plant products. Herbal medicinal plants bear a massive microbial load leading to contamination and mycotoxin, which needs to be considered, and properly controlled using suitable sterilization and decontamination methods. Methods: The main focus of this review is on the definition, advantages, disadvantages and applications of decontamination methods, particularly to show that one must consider the characteristics of the initial sample to be decontaminated. Results: The effects of various methods (ozone, plasma, irradiation) on medicinal herbs and products treated for microbiological decontamination are dependent on factors related to microbial load (i.e., nature and amount of initial contamination), herb/product matrix (i.e., complexity of chemical composition, physical state-solid or liquid) and treatment conditions (i.e., time, irradiation dose, absence or presence of oxygen). In addition, it is important to accept some loss of the chemical compounds , while decreasing microbial load to acceptable limits according to official herbal pharmacopoeias and literature, thus ensuring a final product with quality, safety and therapeutic efficacy. Conclusion: The conclusion, which comes from this contribution, is that herbal medicine has more contaminants than a chemically well-defined drug, thus, good manufacturing practices should be followed.

Penelitian tentang perbandingan profil pelepasan dan kinetika obat secara in vitro dari formula mikrokapsul ekstrak cacing tanah (Lumbricus rubellus) yang dibuat dari Eudragit ® RS dan Eudragit ® RL telah dilakukan. Penelitian ini bertujuan untuk mengetahui mengetahui profil pelepasan dan kinetika obat dari formula mikrokapsul ekstrak cacing tanah (Lumbricus rubellus) yang dibuat dari Eudragit ® RS dan Eudragit ® RL. Formula dibuat dengan menggunakan ekstrak etanol cacing tanah (Lumbricus rubellus) sebagai bahan aktif, Eudragit ® RS dan Eudragit ® RL sebagai polimer dan PVA sebagai surfaktan. Mikrokapsul dibuat dengan variasi polimer Eudragit ® yakni Eudragit ® RS 100 (F1), Eudragit ® RL 100 (F2) dan kombinasi Eudragit ® RS 100: Eudragit ® RL 100 (1: 1). Evaluasi profil pelepasan mikrokapsul dilakukan menggunakan apparatus USP non official dengan metode sampling and separate dan evaluasi kinetika pelepasan obat dilakukan dengan menggunakan perangkat lunak Microsoft Office Excel 2010. Hasil evaluasi profil pelepasan secara in vitro memperlihatkan bahwa masing-masing formula melepaskan protein sebanyak 22,101 ±0,15 % b/b (F1), 28,93 ±0,23 % b/b (F2), dan 32,408 ± 0,31 % b/b (F3). Kinetika pelepasan pada semua formula cenderung mengikuti kinetika Higuchi dengan nilai R untuk masing-masing formula yaitu 0,718 (F1), 0,909 (F2) dan 0,872 (F3). Berdasarkan hasil penelitian maka dapat disimpulkan bahwa kombinasi polimer Eudragit ® memiliki profil pelepasan yang lebih baik dan mekanisme pelepasan obat terjadi secara difusi

BACKGROUND: Carvedilol is an antihypertensive drug use for management of hypertension. It has the half-life of 6 hr and oral bioavailability of 25% due to first pass metabolism. The total daily dose of carvedilol is 25 mg, hence it required frequent dosing. Transdermal patches of carvedilol were prepared for sustained release and improve bioavailability of drug and patient compliance. MATERIALS AND METHODS: Different formulations of reservoir-type transdermal were prepared by varying the amount of Eudragit RL-100 and Eudragit RS-100 by solvent casting method. A 3 2 full factorial design was applied to check the effect of varying the amount of Eudragit-RL 100 (X 1 ) and amount of Eudragit RS-100 (X 2 ) on the responses i.e. tensile strength, percentage drug released in 20 hr (Q 20 ) and Diffusion coefficient (n) as dependent variables. Regression analysis and analysis of variance were performed for dependent variables. In-vitro release data were fitted to various models to ascertain kinetic of drug release. The best selected formulation is subjected to In-Vitro skin permeation and skin irritation study. RESULTS: Batch F 1 was considered optimum batch which contained 300 mg of Eudragit RS-300 and 500 mg of Eudragit RL-100, showed release 95.55% up to 24 hr and was more similar to zero order release kinetics (r 2 =0.985). CONCLUSION: Batch F 1 showed flux of 64. 21 μg/cm 2 /h, hence, the patch area of 1.3 cm 2 would be expected to deliver targeted flux of 83.72μg/cm 2 /h.

Aim: The pharmaceutical industries spend a significant amount on
the advertisement and promotion of their products, of which the
largest division is spent on the visits of sales representatives of
these industries to the physicians. The pharmaceutical sales
representatives educate the physicians about the advancements in
the medical products of their companies and hence are of pivotal
importance in the prescribing behavior of physicians. To assess
their knowledge with respect to their qualification was the
objective of the study.
Methods: A quantitative cross sectional survey was designed
targeting the medical sales representatives (MSRs) in Pakistan
with a probability sampling technique. It was sent to 716 MSRs all
over Pakistan. 691 were returned giving a response rate of 96.5%.
Cross tabulation and Chi square test X2 was used. . Statistical
significance was accepted at p values <0.05.
Results: It was found that almost a third of MSRs (30.9%) were
pharmacist and the rest (69.1%) were non pharmacists. In regard
to their source of knowledge the pharmacist MSR mainly
consulted literature (50%) while the non pharmacist relied on
marketing promotional materials (55%). Majority (92%) of MSR’s
were aware of the pharmacokinetics and pharmacodynamics of
drugs however the 60% of non pharmacist and 4% of the
pharmacist MSR’s were unaware of the adverse drug reactions.
Regarding the beneficence of adverse drug reactions 91% of
pharmacist and 55% of non pharmacist gave negative answer. The
ethical way of promotion was considered knowledge by 92% of
MSR’s, while for black box warnings 90% of pharmacist MSR’s
were aware while 61% of non pharmacist MSR’s were unaware.
Conclusion: It is more beneficial if the MSR has a sound
expertise regarding the therapeutics and well as other vital features
of the drug. A pharmacist is a better choice for this purpose.

The current market for dry powder inhalers (DPIs) has over 20 devices in present use and at least another 30 under development. Clinicians recognize that DPIs are a suitable alternative to pressurized metered dose inhalers (pMDIs) for some patients but the relative performance of devices is often unclear. The problem is compounded by the need to reformulate pMDIs with new propellants, introducing further products to the market with associated variations in performance. This article reviews the DPIs currently available, the driving forces governing new designs, and the claimed advantages of DPIs in the development pipeline.

S-Nicotine, the principal psychoactive constituent of Nicotiana tabacum, underpins addiction to tobacco smoking. Although tobacco consumption is a leading cause of death worldwide, nicotine itself is also proposed to have potential therapeutic benefits for a diverse range of conditions. Nicotine interacts with its cognate receptors in the central nervous system to exert a predominantly modulatory influence, making neuronal nicotinic receptors attractive therapeutic targets. Here, we focus on three natural products as lead compounds for drug discovery programs, nicotine, epibatidine and cytisine, and consider the aims and limitations that shape these drug discovery endeavors.

Do you think it is easier to be starting a career in science now than maybe 50 years ago? Actually it is much more difficult. It was much easier in my day-there was more funding and almost any person who was at all competent didn't have to worry about funding. There are more people in science now and it is much more competitive, the reviewing bodies, with the exception of the Howard Hughes Medical Institute, are very cautious. Before you get supported for a particular project, you have to show that you are able to do it-which is a bit ridiculous. So it is much more difficult today. You have commented that at the NIH you were given the opportunity to explore science in the knowledge that there were always experienced people to help. Do you think this attitude and framework still prevails? That's right! That's even more true now because the field is more structured.When I came along there were no textbooks in the field that were really useful and the number of people doing neurobiology was small. Now there are lots of people that can help you. The issue is more of funding the field than accessibility of colleagues and advice.

BACKGROUND: Curcumin is poorly permeable as well as sparingly soluble drug with varying interpersonal and intrapersonal bioavailability. The main purpose of present work was to develop self Microemulsifying drug delivery system (SMEDDS). Preliminary trials were performed using various oils and surfactants. Pseudo-ternary phase diagrams were constructed to identify the efficientself-emulsification region. The formulation of Curcumin SMEDDS was optimized by a simplex lattice design. The optimal formulation of SMEDDS was comprised of 15% oil (Peceol:Ethyl oleate in 1:1 ratio), 50% surfactant (Labrasol) and 35% co-surfactant (Cremophor EL). The average globule size of optimized SMEDDS containing drug was about 36 nm when diluted in water. No significant variations in globule size and Curcumin content in SMEDDS were observed over a period of 3 months at 40 ±2°C/75 ± 5% RH and 25 ± 3°C (room temperature). In vitro diffusion studies ofoptimized batch using dialysis membrane technique showed more than 95% drug diffusion within 15 min. The data suggested the use of SMEDDS to provide great potential for delivery of Curcumin.

Modulation of the immune system can be addressed through a variety of specific and non-specific approaches. Many agents of synthetic and natural origin have stimulatory, suppressive or regulatory activity. There is growing evidence that drugs or biological agents capable of modulating single pathways or targets are of limited value as immune-related therapies. Systems biology approaches are now gaining more interest compared with monovalent approaches, which can be of limited benefits with complications. This has stimulated interest in the use of ‘cocktails’ of immunodrugs to restore immunostasis. Botanicals are chemically complex and diverse and could therefore provide appropriate combinations of synergistic moieties useful in drug discovery. Here, the importance of traditional medicine in natural product drug discovery related to immunodrugs is reviewed.

Many ion channels are recognized as amenable targets for a range of disease states and conditions. However, the process of discovering drugs is highly influenced by the chemical doability, the biological confidence in rationale of the approach and the 'screenability'. To date, the absence of informative high throughput technologies for ion channel screening has resulted in ion channels remaining a largely unexplored class of drug targets. This, however, is about to change -a large increase in the number of data points per day should be achieved by the introduction of automated 'high throughput' patch clamp machines.

Adapalene (ADP) is a representative of the third retinoids generation and successfully used in first-line acne treatment. ADP binds to retinoic acid nuclear receptors. The comedolytic, anti-inflammatory, antiproliferative, and immunomodulatory are the known ADP effects. Its safety profile is an advantage over other retinoids. ADP recently was found to be effective in the treatment of several dermatological diseases and photoaging besides the utility in the treatment of acne vulgaris. New biological effects of adapalene with therapeutic potential are highlighted in this review paper. Thus, adapalene could be a valuable therapeutic drug into the treatment of several types of cancer. Additionally, some neurodegenerative diseases could be treated with a suitable formulation for intravenous administration. The antibacterial activity against methicillin-resistant Staphylococcus aureus of an analogue of ADP has been proven. In different therapeutic schemes, ADP is more effective in combina...

The information age has made the electronic storage of large amounts of data effortless.The proliferation of documents available on the Internet, corporate intranets, news wires and elsewhere is overwhelming. Search engines only exacerbate this overload problem by making increasingly more documents available in only a few keystrokes. This information overload also exists in the biomedical field, where scientific publications, and other forms of text-based data are produced at an unprecedented rate. Text mining is the combined, automated process of analyzing unstructured,natural language text to discover information and knowledge that are typically difficult to retrieve. Here, we focus on text mining as applied to the biomedical literature. We focus in particular on finding relationships among genes, proteins, drugs and diseases, to facilitate an understanding and prediction of complex biological processes. The LitMiner™ system, developed specifically for this purpose; is described in relation to the Knowledge Discovery and Data Mining Cup 2002, which serves as a formal evaluation of the system. www.drugdiscoverytoday.com REVIEWS RESEARCH FOCUS

Large-scale comparative analysis of drug-target polymorphism structures enables the rational design of next generation 'super drugs' -drugs that are less prone to development of drug resistance or that work for the largest possible fraction of the patient population. Furthermore, knowledge of the drug-target-shape repertoire that exists within the patient population enables predictions of likely clinical trial outcomes and response rates for drug efficacy. This gives information on the optimal drug candidates before the initiation of clinical trials. The economic impact of incorporating pharmacogenomics insights early on in the drug discovery process will be substantial and will afford significant competitive advantages to companies that successfully incorporate this technology.

Purpose: Natural gums are widely used in pharmaceuticals, food industry and cotton industry because of its easy availability, low cost and devoid of toxicity. Current study focuses on the extraction of gum from tamarind seed and subjected to toxicity studies for its safety. Rheological characters like thixotropy and viscosity of tamarind gum was investigated and compared with other natural gums. Methods: Paracetamol I.P. suspensions were prepared using acacia, tragacanth, and tamarind gum as suspending agents. Comparative studies of suspending characters of natural gums were carried out. Results: No toxic character was investigated. Tamarind gum was found to show a better thixotropic behavior and suspending property compared to tragacanth and acacia. Conclusion: Above study revealed that tamarind gum can be a good source as pharmaceutical adjuvant specifically a suspending agent.

Advances in bioinformatics and protein modeling algorithms, in addition to the enormous increase in experimental protein structure information, have aided in the generation of databases that comprise homology models of a significant portion of known genomic protein sequences. Currently, 3D structure information can be generated for up to 56% of all known proteins. However, there is considerable controversy concerning the real value of homology models for drug design. This review provides an overview of the latest developments in this area and includes selected examples of successful applications of the homology modeling technique to pharmaceutically relevant questions. In addition, the strengths and limitations of the application of homology models during all phases of the drug discovery process are discussed.

Vaccinology has experienced a dramatic resurgence recently, as traditional methodologies of using attenuated live pathogens or inactivated whole pathogens have been either ineffective or are not an acceptable risk for several disease targets, including HIV and Hepatitis C. Gene-based vaccines can stimulate potent humoral and cellular immune responses, and viral vectors might be an efficient strategy for both delivery of antigen-encoding genes, as well as facilitating and enhancing antigen presentation. Vectors derived from diverse viruses with distinct tropism and gene expression strategies have been developed, and are being evaluated in preclinical and clinical vaccine studies. Virus-based vaccines represent a promising approach for vaccines against infectious and malignant disease.

Combinatorial biosynthesis utilizes the enzymes from antibiotic (and other natural product) biosynthetic pathways to create novel chemical structures. The manipulation of modular polyketide synthases (PKSs) has been the major focus of this effort and has led to the production of, for example, several erythromycin analogs. Many new tools for manipulating and studying these multifunctional enzymes have been developed. These include multiple hosts and expression systems, enzymology tools for in vitro study, and ways to engineer pre-PKS and post-PKS pathways. The result is more rational and faster methods of engineering new compounds for the development of chemotherapeutic agents from natural products. The most significant recent advances in combinatorial biosynthesis are outlined.

Antimicrobial resistance is the ability of a microorganism to tolerate antimicrobial treatments. It is a problem in Africa, due to the very fact that folks are susceptible to infections and that they have an enormous appetite for antibiotics because they believe it is a robust medicine that results in high consumption rates. Knowledge of local and regional antimicrobial resistance is vital for deciding. However, surveillance capacity for antimicrobial resistance is lacking throughout sub-Saharan countries and current antimicrobial resistance data are sparse. This review sought to deal with this gap by summarizing, assessing, and documenting all available data on this public issue within the sub-Saharan countries for the reader. Data for this review were collected from an online database. Searches were conducted using one health, antibacterial, policies, regulation, antimicrobial resistance, and sub-Saharan countries as a keyword by inserting into search engines. One health approach collaborating with other stakeholders, and regulatory agents working together to optimize the health of animals, humans, foodstuffs, and the environment by combating antimicrobial resistance. Thus, the implementation of one health approach, and regulatory perspective in combating antimicrobial resistance should be critically recognized as a framework for addressing this global issue. Therefore, the target of the present seminar was to review the one health approach, and regulatory perspective in combating antimicrobial resistance in sub-Saharan countries.

Apoptosis or programmed cell death is a set of ordered events that enables the selective removal of cells from tissue and is essential for homeostasis and proper function of multicellular organisms. Components of this signaling network, which include ligands, such as CD95, tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand, as well as downstream molecules, such as caspases, Bcl-2 family

In this study, the combination of etodolac and colchicine was studied for its anti-inflammatory activity. Thirty rats of either sex were divided into five groups' viz. control (received vehicle); an etodolac alone (received 46 mg/kg etodolac); colchicine alone (received 0.23 mg/kg colchicine), low dose combination of etodolac and colchicine (received 23 mg/kg etodolac plus 0.11 mg /kg colchicine) and high dose combination of etodolac and colchicine (received 46 mg/kg etodolac plus 0.23 mg/kg colchicine) of six animals each. The anti-inflammatory activity of the drugs was tested in carrageenan-induced rat-paw oedema. The high dose combination of etodolac (46 mg/kg) and colchicine (0.23 mg/kg) showed 85.29 % inhibition and low dose combination of etodolac (23 mg/kg) and colchicines (0.11 mg/kg) showed 82.35% inhibition on carrageenan induced rat paw oedema. The results of this study reveal that high dose combination of etodolac and colchicine has significantly higher (p<0.05) anti-inflammatory activity than etodolac or colchicine alone.

Objective: To evaluate anti-inflammatory potential of rind extract of Punica granatum by in-vitro anti-inflammatory model and its phytochemical evaluation. Method: The fractionation of methanolic extract of Punica granatum rind was done using various solvents and evaluated for anti-inflammatory activity using in-vitro human red blood cell (HRBC) membrane stabilization method and its phytochemical study. Results: The in-vitro membrane stabilizing test showed that butanol, nhexane and aqueous extracts have potent anti-inflammatory activity which were 42.66%, 14.1% and 28% protection, respectively as compared to Standard drug. The potency of the rind extracts of PG were compared with standard diclofenac in stabilization test and which showed 81.76% protection in in-vitro HRBC membrane stabilization method. The extract showed the dose dependent anti-inflammatory activity. Conclusions: The present investigation has confirmed the antiinflammatory activity of fractions of methanolic extract of Punica granatum rind due to presence of alkaloids, steroids, terpinoids for the first time and provided the pharmacological evidence in the favour of traditional uses of Punica granatum as an anti-inflammatory agent.

Adapalene (ADP) is a representative of the third retinoids generation and successfully used in first-line acne treatment. ADP binds to retinoic acid nuclear receptors. The comedolytic, anti-inflammatory, antiproliferative, and immunomodulatory are the known ADP effects. Its safety profile is an advantage over other retinoids. ADP recently was found to be effective in the treatment of several dermatological diseases and photoaging besides the utility in the treatment of acne vulgaris. New biological effects of adapalene with therapeutic potential are highlighted in this review paper. Thus, adapalene could be a valuable therapeutic drug into the treatment of several types of cancer. Additionally, some neurodegenerative diseases could be treated with a suitable formulation for intravenous administration. The antibacterial activity against methicillin-resistant Staphylococcus aureus of an analogue of ADP has been proven. In different therapeutic schemes, ADP is more effective in combina...

Pharmaceutical companies are facing an urgent need to both increase their lead compound and clinical candidate portfolios and satisfy market demands for continued innovation and revenue growth. Here, we outline an emerging approach that attempts to facilitate and alleviate many of the current drug discovery issues and problems. This is, in part, achieved through the systematic integration of technologies, which results in a superior output of data and information, thereby enhancing our understanding of biological function, chemico-biological interactions and, ultimately, drug discovery. Systems biology is one new discipline that is positioned to significantly impact this process.

Directed evolution is a broadly applicable technology platform that is ideally suited to address the need for protein optimization and to fully exploit the therapeutic potential of biologics. The approach takes advantage of the remarkable structural and functional plasticity of proteins and permits the rapid remodeling of biologics into new entities with improved functions. The ability to ameliorate virtually any characteristic of a protein can translate into significant clinical benefits, including decreased immunogenicity, higher potency, greater efficacy and improved safety profile, and can considerably increase the probability of successfully developing and commercializing biotherapeutics.

Arthritis is a common disease in which the end-point results in joint replacement surgery. This article reviews the use of nutraceuticals as alternative treatments for pathological manifestations of arthritic disease. The efficacy of fish oils (e.g. cod liver oil) in the diet has been demonstrated in several clinical trials, animal feeding experiments and in vitro models that mimic cartilage destruction in arthritic disease. In addition, there is some evidence for beneficial effects of other nutraceuticals, such as green tea, herbal extracts, chondroitin sulphate and glucosamine. However, in most cases, there is little scientific evidence at the cellular and molecular levels to explain their mechanisms of action.

The intimate connection, both physical and biochemical, between blood vessels and bone cells has long been recognized. Genetic, biochemical, and pharmacological studies have identified and characterized factors involved in the conversation between endothelial cells (EC) and osteoblasts (OB) during both bone formation and repair. The longawaited FDA approval of two growth factors, BMP-2 and OP-1, with angiogenic and osteogenic activity confirms the importance of these two processes in human skeletal healing. In this review, the role of osteogenic factors in the adaptive response and interactive function of OB and EC during the multi-step process of bone repair will be discussed.

-exchange resins (IER), or ionic polymer networks, have received considerable attention from pharmaceutical scientists because of their versatile properties as drug-delivery vehicles. In the past few years, IER have been extensively studied in the development of novel drug-delivery systems (DDSs) and other biomedical applications. Some of the DDSs containing IER have been introduced into the market. In this review, the applications of IER in drug delivery research are discussed.

Could you describe the early defining events that shaped your development as an entrepreneurial scientist? When I was getting my doctorate, there was a fortuitous convergence of interest and opportunity in that I was working on a group of toxins, such as ricin, that were just achieving commercial potential. Developing a market for these toxins involved discovering new toxins with novel properties. Because these compounds are primarily found in the leaves, seeds or roots of plants from equatorial jungles, I was able to build a successful business, Inland Laboratories, while indulging a long-held wanderlust. Did you have a particular role model in this respect? Everybody who started a biotechnology business in the early 1980s looked to the founders of Genentech. When I was getting my doctorate at Southwestern Medical School, entrepreneurial activities in the biotechnology business were not considered an option. One would either teach at a medical school or university, or go into research at a pharmaceutical company. The people at Genentech started with an idea update feature

Fibroblast growth factors (FGFs) are broad-range morphogens that have significant functional roles in early and late embryonic development. For example, genetic analyses in mice have demonstrated that FGFs play crucial roles in mesoderm induction and in lung and brain development. Furthermore, FGFs are thought to be implicated in renewal processes in the adult by promoting neuronal stem cell survival, neuron migration, wound healing and tissue repair (reviewed in ).