Pharmaceutical Technology

Binding a critical pentapeptide region on the scaffolding protein filamin A regulates signaling of mu opioid receptors so that their activation should not result in the opioid tolerance, dependence and addiction associated with current opioid painkillers. Additionally, we show that compounds that bind this site on filamin A reduce release of inflammatory cytokines. PTI-609 is a new chemical entity that binds filamin A with picomolar affinity and also activates opioid receptors via a novel binding domain. PTI-609 and analogs have similar analgesic efficacy to morphine by oral administration in mice, provide some anti-inflammatory activity in the rat collagen-induced arthritis model, and show no conditioned place preference at analgesic doses, suggesting no potential for abuse and addiction. PTI-609 was designed after discovering filamin A as the high-affinity target of naltrexone or naloxone. Combined with opiates, ultra-low-dose naloxone or naltrexone can enhance and prolong the analgesia of the opiate alone and prevent or attenuate opioid tolerance, dependence and addictive properties. We will review here the mechanism of action of ultra-low-dose naltrexone and naloxone, the discovery of filamin A as their high-affinity target, and the rationale as to why the current, dualfunction new chemical entity should not only be easier to develop but also more consistently efficacious than opioids combined with ultra-low-dose naltrexone. This new class of compounds, as well as the concept, screening assay and pharmacophore model, are covered in a family of recent patent applications.

Bacterial endotoxin is the lipopolysaccharide component of the cell wall of Gram-negative bacteria, together with other cellular material that combines to form an endotoxin complex. Endotoxin is pyrogenic and it presents a risk to patients who are administered intravenous and intramuscular preparations.1Thus bacterial endotoxins pose a risk to many pharmaceutical processes and, where not controlled, to the finished products. There are different methods for endotoxin removal. These include depyrogenation,2 such as dry-heat processes applied to glassware, and rinsing,3 as might be applied to closures. These areas receive reasonable coverage within the pharmaceutical sector. Areas that are actively discussed within biotechnology fields but which receive less attention in the wider pharmaceutical context are steps to remove endotoxin bound to protein. This article considers some of the biotechnological applications for endotoxin removal.

It has been previously described that when a sample's particle size is determined using different sizing techniques, the results can differ considerably. The purpose of this study was to review several in-process techniques for particle size determination (Spatial Filtering Velocimetry, Focused Beam Reflectance Measurements, Photometric Stereo Imaging, and the Eyecon Ò technology) and compare them to well-known and widespread off-line reference methods (laser diffraction and sieve analysis). To start with, a theoretical explanation of the working mechanism behind each sizing technique is presented, and a comparison between them is established. Secondly, six batches of granules and pellets (i.e., spherical particles) having different sizes were measured using these techniques. The obtained size distributions and related D 10 , D 50 , and D 90 values were compared using the laser diffraction wet dispersion method as reference technique. As expected, each technique provided different size distributions with different D values. These dissimilarities were examined and explained considering the measurement principles behind each sizing technique. The particle property measured by each particle size analyzer (particle size or chord length) and how it is measured as well as the way in which size information is derived and calculated from this measured property and how results are presented (e.g., volume or mass distributions) are essential for the interpretation of the particle size data.

"""Excipients are the integral part of pharmaceutical products development to achieve desired product profile(stability and efcacy). This review deals with understanding of the physicochemical properties of excipients used
in parenteral formulation development for solution, suspension and lyophilized drug products. However, in spite of proper excipients selection, judicious use during formulation manufacturing process based on their critical properties is also important to avoid negative effects such as loss of drug solubility, activity and stability. This paper deals with proper selection of excipients in lyophilized drug products which gives high critical temperature, good bulking properties avoiding melt back and collapse with improved dried product appearance. We have also emphasized on appropriate selection of excipients for solution, suspension injectable dosage forms and linking their physiochemical properties with optimum manufacturing method with suitable case studies. This review will highlight various excipient related issues optimizing product performance with documented references and practical approaches based on scientific justification. The reader will gain better understanding of excipients complexity during stability studies and resolving problems with practical approach."

Laboratory Information System (LIS) streamlines workflow in the laboratory and eliminates time-consuming paperwork. The business today is getting increasingly pressured to be more productive and efficient with less traditional resources. If we look at a typical production process, for instance, the level of automation and optimization that has permeated into the production floor is quite astounding. Many industries have had a tremendous impact in bringing to the market the automation and optimization solutions to streamline -the production floor. The other ends of the spectrum are the back-office transaction oriented processes like Inventory Management, Materials Management, Financials and so on, Therefore a lab’s ability to process data quickly and its ability to disseminate that information efficiently throughout the plant is vital for the success of the production process. Laboratory Information Management System (LIMS) can help in managing the information flow within the lab and can be the modus operandi of connecting the lab with the rest of the organization. For instance, imagine all the information that is generated in a lab.

Environmental monitoring is a programme which evaluates the cleanliness of the manufacturing environment; the effectiveness of cleaning and disinfection programmes; and the operational performance of environmental controls. As such, pharmaceutical manufacturers of both sterile and non-sterile products, as well as medical devices, are required to demonstrate that manufacturing processes and procedures minimise any potential contamination to the product from the manufacturing environment. Contamination can arise from a number of sources: water, air, surfaces and personnel, each of which poses a potential risk to product.

Cleanroom contamination can arise from a number of sources. Most contamination within the pharmaceutical facility can be traced to humans working in cleanrooms. The paper discusses staff gowning and personnel behavior in pharmaceutical cleanrooms, and how cleanroom risk can be minimized. The human skin ecosystem is discussed. The Human Microbiome Project (HMP) from the US NIH characterized microorganisms found in association with both healthy and diseased humans. Information from this project has great impact on cleanroom activities including gowning practices. Topics associated with cleanroom garments are discussed including fabric types,

Compressed gas sampling for microorganisms is an important part of contamination control assessment.  This paper addresses topics related to microbial assessment of compressed gases.  These include gas purity including moisture considerations, sterile filtration, compressed gas standards, microbial contamination, microbial survival, sampling and testing requirements, instrumentation, and various sampling considerations including growth medium choice and frequency, and reporting requirements.

Cleanrooms are highly controlled environments, defined by
the air quality, and where certain physical and microbiological
requirements need to be met. Air quality is achieved through
a combination of airborne particulate control, such as through
high efficiency particulate air filters; high fresh air rates (air
movement and air changes); clean-up (or ‘recovery’) times;
pressure differentials, which concerns air direction;
temperature and humidity control (where necessary); cleaning
and disinfection; and staff behaviours and gowning. The
requirements for air quality, and the associated physical
aspects designed to achieve this, are contained within the
international standard ISO 14644.

Dry powder formulations are often composed of fine drug particles and coarser carrier particles, typically alpha-lactose monohydrate. However, the performance of a powder formulation may be highly dependent on the lactose quality and source. This study investigated the characteristics of lactose that influence the drug-to-carrier interaction and the performance of lactose-based dry powder inhaler formulations. The selected lactoses differed in the preparation processes and the content of fine lactose particles. Efficiency testing was done using fluticasone propionate and terbutaline sulphate as model drugs. Inverse gas chromatography was used to determine the surface heterogeneity distribution of different energy sites of the lactose and to understand the mechanism by which the fine carrier particles can improve the performance of dry powder inhalers. To assess the adhesion of respirable-sized drug to carrier particles, a simple method was developed based on aspiration and consideri...

Molecular Pharming, the production of recombinant pharmaceuticals through plant biotechnology, has the potential to transform the biologics sector of the pharmaceutical industry. More fascinating however, is how it might be used to improve access to modern medicines, and improve health of the poor in developing countries and emerging economies. Although improving global health through molecular pharming has been discussed for at least two decades, little progress has actually been made. In this manuscript, a four point plan is described to maximise the opportunity for molecular pharming to provide solutions. These are (i) to identify and prioritise important drug targets that are relevant to the poor; (ii) to support research and development partners in low to middle income countries to develop local expertise, transfer technology and build capacity; (iii) to increase collaboration between regulatory bodies to enable national regulatory frameworks to be developed in low to middle income countries; and (iv) to promote intellectual property management approaches that include socially responsible licensing. An existing case study is described to illustrate how this might be achieved. 2013) Realising the value of plant molecular pharming to benefit the poor in developing countries and emerging economies. Plant Biotechnol. J.,

Vial ''Fogging'' is a phenomenon observed after lyophilization due to drug product creeping upwards along the inner vial surface. After the freeze-drying process, a haze of dried powder is visible inside the drug product vial, making it barely acceptable for commercial distribution from a cosmetic point of view. Development studies were performed to identify the root cause for fogging during manufacturing of a lyophilized monoclonal antibody drug product. The results of the studies indicate that drug product creeping occurs during the filling process, leading to vial fogging after lyophilization. Glass quality/ inner surface, glass conversion/vial processing (vial ''history'') and formulation excipients, e.g., surfactants (three different surfactants were tested), all affect glass fogging to a certain degree. Results showed that the main factor to control fogging is primarily the inner vial surface hydrophilicity/hydrophobicity. While Duran vials were not capable of reliably improving the level of fogging, hydrophobic containers provided reliable means to improve the cosmetic appearance due to reduction in fogging. Varying vial depyrogenation treatment conditions did not lead to satisfying results in removal of the fogging effect. Processing conditions of the vial after filling with drug product had a strong impact on reducing but not eliminating fogging.

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Influenza virus-like particle vaccines are one of the most promising ways to respond to the threat of future influenza pandemics. VLPs are composed of viral antigens but lack nucleic acids making them non-infectious which limit the risk of recombination with wild-type strains. By taking advantage of the advancements in cell culture technologies, the process from strain identification to manufacturing has the potential to be completed rapidly and easily at large scales. After closely reviewing the current research done on influenza VLPs, it is evident that the development of quantification methods has been consistently overlooked. VLP quantification at all stages of the production process has been left to rely on current influenza quantification methods (i.e. Hemagglutination assay (HA), Single Radial Immunodiffusion assay (SRID), NA enzymatic activity assays, Western blot, Electron Microscopy). These are analytical methods developed decades ago for influenza virions and final bulk influenza vaccines. Although these methods are time-consuming and cumbersome they have been sufficient for the characterization of final purified material. Nevertheless, these analytical methods are impractical for in-line process monitoring because VLP concentration in crude samples generally falls out of the range of detection for these methods. This consequently impedes the development of robust influenza-VLP production and purification processes. Thus, development of functional process analytical techniques, applicable at every stage during production, that are compatible with different production platforms is in great need to assess, optimize and exploit the full potential of novel manufacturing platforms.

Oral dosage forms are the most popular way of taking medication, despite having some disadvantages compared with other methods like risk of slow absorption of the medicament, which can be overcome by administering the drug in liquid form, therefore, possibly allowing the use of a lower dosage. However, instability of many drugs in liquid dosage form limits its use. Effervescent technique can be used as alternate to develop a dosage form which can accelerate drug disintegration and dissolution, is usually applied in quick release preparations. Along with the development of new pharmaceutical technique, effervescent tablet are more and more extensively to adjust the behaviour of drug release, such as in sustained and controlled release preparations, pulsatile drug delivery systems, and so on. This review demonstrated the new applying of effervescent technique in effervescent tablets. Keywords: Effervescent Tablet, Sustained release, Floating Delivery System

The moderate heat treatment of amphotericin B (AmB) in its micellar form (M-AmB) results in superaggregates (H-AmB) that present a substantially lower toxicity and similar activity. The aim of this work was to evaluate the H-AmB behavior after a freeze-drying process. H-AmB and M-AmB micelles were evaluated before and after freeze-drying concerning their physicochemical and biological properties by spectrophotometry and activity/toxicity assay, respectively. Four concentrations of M-AmB and H-AmB were studied aiming to correlate their aggregation state and the respective biological behavior: 50 mg L −1 , 5 mg L −1 , 0.5 mg L −1 , and 0.05 mg L −1. Then, potassium leakage and hemoglobin leakage from red blood cells were used to evaluate the acute and chronic toxicity, respectively. The efficacy of M-AmB and H-AmB formulations was assessed by potassium leakage from Candida albicans and by the broth microdilution method. After heating, in addition to an evident turbidity, a slight blueshift from 327 to 323 nm was also observed at the concentrations of 50 and 5 mg L −1 for H-AmB. Additionally, an increase in the absorbance at 323 nm at the concentration of 0.5 mg L −1 was detected. Concerning the toxicity, H-AmB caused significantly lower hemoglobin leakage than M-AmB. These results were observed for H-AmB before and after freeze-drying. However, there was no difference between H-AmB and M-AmB concerning their activity. Accordingly, the freeze-drying cycle did not show any influence on the behavior of heated formulations, highlighting the suitability of such a method to produce a new AmB product with a long shelf life and with both greater efficiency and less toxicity.

The use of medicines is an irreplaceable necessity in healthcare delivery. Application of advancing technology, especially the oral film techniques in pharmaceutical production has resulted in medicine availability in a trendy, readily acceptable and usable form, oral films. Although many literature abound on oral film delivery systems, there is paucity of work on recent incorporation of nanotechnology concepts and the potentials of this delivery system in improving medication adherence. Thus this work focuses on bridging this obvious gap. It reviews published works on the oral film technology, profiling recent advances in the nanoparticles incorporated into films, and necessary considerations in such formulations. It also explores oral films as a delivery system for improved adherence. Online search for articles on oral films production, marketed nanoparticle-based oral films, and the extensiveness of medication non-adherence was carried out using websites of researchgate, google search, film manufacturer's websites, google scholar and pubmed. Search terms used were 'marketed oral films', 'available medicines as oral films', 'nanotechnology in oral film production', 'oral film techniques', 'oral films manufacture + disease condition' and 'medicine adherence'. Articles were sorted on the basis of currency and practicality of information. The market space of oral film is growing steadily. Present use of oral film technology in delivering antipsychotics, antihistamines and analgesics is well received. Many drugs are currently incorporated into films in nano-sized forms to improve dissolution, bioavailability and effectiveness as revealed by the search. More can be achieved if this technology is extended to cover other classes of drugs such as antihypertensives, antiulcers and agents indicated for other chronic conditions. Fully exploring the unique features of the conventional oral films dosage forms and those embedded with nanoparticulate drug forms, therein lies the potentials to contribute to significant improvement in medication adherence even in chronic conditions.

Progesterone rapidly dissolves in an aqueous solution containing hydroxypropyl-b-cyclodextrin (HPBCD) at 1:2 molar ratio, forming a soluble inclusion complex. After filtration and freeze-drying of the final solution, the final powder was examined by SEM, DSC, TGA, XRD, Raman, and FTIR spectroscopy. Experimental results confirm that an inclusion complex exists in the solid state and possible structure of the complex is briefly discussed. ß

The brain is a delicate organ, and nature has very efficiently protected it. The brain is shielded against potentially toxic substances by the presence of two barrier systems: the blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB). Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Despite aggressive research, patients suffering from fatal and/or debilitating central nervous system (CNS) diseases, such as brain tumours, HIV encephalopathy, epilepsy, cerebrovascular diseases and neurodegenerative disorders, far outnumber those dying of all types of systemic cancers or heart diseases. The abysmally low number of potential therapeutics reaching commercial success is primarily due to the complexity of the CNS drug development. The clinical failure of many probable candidates is often, ascribable to poor delivery methods which do not pervade the unyielding BBB. It restricts the passive diffusion of many drugs into the brain and constitutes a significant obstacle in the pharmacological treatment of central nervous system (CNS) disorders. General methods that can enhance drug delivery to the brain are, therefore, of great pharmaceutical interest. Various strategies like non-invasive methods, including drug manipulation encompassing transformation into lipophilic analogues, prodrugs, chemical drug delivery, carrier-mediated drug delivery, receptor/vector mediated drug delivery and intranasal drug delivery, which exploits the olfactory and trigeminal neuronal pathways to deliver drugs to the brain, are widely used. On the other hand the invasive methods which primarily rely on disruption of the BBB integrity by osmotic or biochemical means, or direct intracranial drug delivery by intracerebroventricular, intracerebral or intrathecal administration after creating reversible openings in the head, are recognised. Extensive review pertaining specifically, to the patents relating to drug delivery across the CNS is currently available. However, many patents e.g. US63722506, US2002183683 etc., have been mentioned in a few articles. It is the objective of this article to expansively review drug delivery systems for CNS by discussing the recent patents available.

The objective of the current study was to develop and validate a simple, precise and accurate isocratic stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay method for the determination of spironolactone and furosemide in solid pharmaceutical dosage forms. Isocratic RP-HPLC separation was achieved on an SGE 150 × 4.6 mm SS Wakosil II 5C8RS 5-μm column using a mobile phase of acetonitrile-ammonium acetate buffer (50:50, v/v) at a flow rate of 1.0 mL/min. The detection was carried out at 254 nm using a photodiode array detector. The drug was subject to oxidation, hydrolysis, photolysis and heat to apply stress conditions. The method was validated for specificity, linearity, precision, accuracy, robustness and solution stability. The method was found to be linear in the drug concentration range of 40-160 µg/mL with correlation coefficients of 0.9977 and 0.9953 for spironolactone and furosemide, respectively. The precision (relative standard deviation; RSD) among a six-sample preparation was 0.87% and 1.1% for spironolactone and furosemide, respectively. Repeatability and intermediate precision (RSD) among a six-sample preparation were 0.46% and 0.20% for spironolactone and furosemide, respectively. The accuracy (recovery) was between 98.05 and 100.17% and 99.07 and 100.58% for spironolactone and furosemide, respectively. Degradation products produced as a result of stress studies did not interfere with the detection of spironolactone and furosemide; therefore, the assay can be considered to be stability-indicating.

The in vitro dissolution of albendazole from three different commercially available products (200 mg tablets) was studied using U.S. Pharmacopeia (USP) Apparatus 2 and USP Apparatus 4 in order to compare the release performance of the drug in two essentially different dissolution systems. For both cases, 0.1 N HCl was used as dissolution medium. Only the reference product and one of the generic products studied met the 80% USP 24 specification for albendazole dissolved at 30 min, using USP Apparatus 2. Although the reference product reached 80% of albendazole dissolved at 30 min when Apparatus 4 was used, the generic products' dissolution performance was markedly reduced in this system. Though dissolution rate was slower using Apparatus 4, the total quantity of albendazole dissolved from the reference product, represented by area under the dissolution profile, was practically the same regardless of the system used. Dissolution kinetics of albendazole was adequately described by Weibull's function for all the products. The dissolution time (t d ) derived from data fitting to this function showed significant differences among the products studied. Data analysis based on analysis of variance (ANOVA) showed nonequivalence among the dissolution profiles of generic products compared with the reference product either with the dissolution vessel system or the flow-through cell, as well as nonequivalence among the dissolution profiles using both apparatuses with the same product. Though differences in the dissolution profiles for generic products against the reference product in both systems were found, USP Apparatus 4 showed higher discriminative capacity in differentiating the release characteristics of the products tested.

. An isocratic high-performance liquid chromatography (HPLC) procedure was developed for the dissolution rate studies and quantitative determination of valdecoxib in solid dosage forms and in active pharmaceutical ingredient. HPLC separation was carried out by reversed phase chromatography on a Syn-ergi ® fusion C 18 column (150 mm x 4.6 mm i.d.; 4 µm particle size), held at 30 ºC. The mobile phase con-sisted of water, pH 7.0/acetonitrile (52:48, v/v), run at a flow rate of 1.0 mL/min and with UV detection at 210 nm. Method validation investigated parameters such as the linearity (r 2 =0.9999), range, precision, ac-curacy, robustness and specificity. The method yielded good results with a quantitation limit of 50 ng/mL and a detection limit of 10 ng/mL. The dissolution test conditions and the dissolution medium was chosen as 0.5% of sodium lauryl sulfate in water at a stirring rate of 75 rpm. The described method can be successful-ly applied for the analysis of tablets, active pharm...

Microbubbles system is a newly invented non-invasive technique in which, in the presence of ultrasound waves or harmonic sounds
micropores shrinks and agitated to produce micro bubbles within the applied area. These bubbles have the capability to target any perfused
tissues within our body. Recently it was postulated that due to its narrow size range (1 to 10μm vesicular diameter) it can get easily engulf
by phagocytic blood cells which can be very effective on lymphocytic cancer. Micro bubbles are prepared by using mechanical agitation,
ultrasonication, pressurized gas-liquid mixing system etc. Micro bubbles are made up of a monolayer of protein shells, lipid shells, surfactant
shells, polymer shells, Polyelectrolyte multilayer shells. Initially, microbubbles are used as diagnostic tools but due to its versatility of uses and properties of surface conjugation of proteins, genes, micro molecular nutrients, drugs slowly it’s becoming a therapeutic delivery tool. ALBUNEX® (GE Healthcare) was the first albumin conjugated micro bubble which was been approved by US-FDA. Recently importance is been given for brain targeting using Micro bubble carrier system. It was observed that using passive and active transport micro streamed bubbles can able to transport through Blood Brain Barrier (BBB). It is very important to give more importance to its stability and canonization of globules for more industrial acceptability.

In the past year, new approaches to control high cell density fermentations, molecular strategies coupled with fermentation technology, and updated traditional strategies have been used to overproduce important biological products. The most significant advances include new implementation of control strategies for feeding high cell density fermentations as well as the continued development of alternative Gram-positive bacterial expression systems.

Differences in the dynamics of powder densification between eccentric and rotary machine were pointed out by compressing at different compression pressures microcrystalline cellulose, lactose monohydrate and dicalcium phosphate dihydrate and recovering the corresponding stress/strain data in both machines equipped to monitor punches displacement and compression forces. Heckel plots were then obtained from these stress/strain data.

Melibiose monohydrate has shown promise when employed as a pharmaceutical excipient, but its physical properties have not been adequately characterized. Therefore, two different melibiose monohydrate batches were analyzed as received or after storage under different relative humidity (RH) atmospheres. The particle size distributions and specific surface areas of the two batches were shown to differ considerably, which also had an effect on their water sorption tendencies and on the intermolecular structure of melibiose after storage. The relatively large primary particles that were more abundant in one of the batches were shown to possess a porous surface structure, and water evaporation from them occurred in two phases when heated. Furthermore, storing the batch with smaller mean particle size under dry conditions affected the crystal structure and molecular vibrations of the sample more than in the case of the batch with larger mean particle size. It was concluded that the physical properties of melibiose monohydrate after storage at different RH atmospheres is largely governed by the primary particle size and porosity.

Purpose (1) To determine the effect of solution pH before lyophilization, over the range of 1.5 to 10, on the salt and polymorphic forms of glycine crystallizing in frozen solutions and in lyophiles. (2) To quantify glycine crystallization during freezing and annealing as a function of solution pH before lyophilization. (3) To study the effect of phosphate buffer concentration on the extent of glycine crystallization before and after annealing. Materials and Methods Glycine solutions (10% w/v), with initial pH ranging from 1.5 to 10, were cooled to −50°C, and the crystallized glycine phases were identified using a laboratory X-ray source. Over the same pH range, glycine phases in lyophiles obtained from annealed solutions (0.25, 2 and 10% w/v glycine), were characterized by synchrotron X-ray diffractometry (SXRD). In the pH range of 3.0 to 5.9, the extent of glycine crystallization during annealing was monitored by SXRD. Additionally, the effect of phosphate buffer concentration (50 to 200 mM) on the extent of glycine crystallization during freezing, followed by annealing, was determined. Results In frozen solutions, β-glycine was detected when the initial solution pH was ≥ 4. In the lyophiles, in addition to β- and γ-glycine, glycine HCl, diglycine HCl, and sodium glycinate were also identified. In the pH range of 3.0 to 5.9, decreasing the pH reduced the extent of glycine crystallization in the frozen solution. When the initial pH was fixed at 7.4, and the buffer concentration was increased from 50 to 200 mM, the extent of glycine crystallization in frozen solutions decreased with an increase in buffer concentration. Conclusion Both solution pH and solute concentration before lyophilization influenced the salt and polymorphic forms of glycine crystallizing in frozen solutions and in lyophiles. The extent of glycine crystallization in frozen solutions was affected by the initial pH and buffer concentration of solutions. The high sensitivity of SXRD allowed simultaneous detection and quantification of multiple crystalline phases.

The aim of the present study was to formulate and evaluate Metformin HCl microspheres to produce a drug delivery system with better pharmaceutical and therapeutic properties. Metformin HCl microspheres were prepared by using ethyl cellulose as a release retardant polymer by solvent evaporation method .Formulations F1, F2 and F3 were prepared using ethyl cellulose in the drug polymer ratio of 1:1, 1:2 and 1:3. A plasticizer (N-dibutyl phthalate) was added in formulations F4,F5 and F6 .The prepared microspheres were evaluated for the parameters like Percentage yield, Particle size analysis, Micromeritic properties like angle of repose, bulk density, tapped density, compressibility index, Hausner’s ratio, melting point determination, drug content estimation, microencapsulation efficiency and in vitro drug release studies. The in vitro release of Metformin HCl was slow and extended over longer period of time. As the concentration of polymer was increased, the drug release was decreased. The drug release was found to be slow in formulations F4, F5 and F6 when compared to F1, F2 and F3. Thus the study clearly indicated a promising potential of sustained release Metformin HCl microspheres containing ethyl cellulose as rate controlling polymer for effectively treating diabetes mellitus.

A method of producing self-emulsifying pellets by wet granulation of powder mixture composed of microcrystalline cellulose, lactose and nimesulide as model drug with a mixture containing mono-and di-glycerides, polisorbate 80 and water, in a 10-l high shear mixer has been investigated.

Abstract: Mesalamine is an anti-inflammatory drug used in the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. In contrast to the immediate-release oral solid dosage forms, mesalamine should exhibit delayed release achieved through an enteric coating intended to resist gastric fluid and release the drug into the colon region. The lack of application of the coating as well as the guarantee of the quality of the coating may result in aggravation of the disease due to the lack of desired therapeutic effect, since the drug may undergo dilutions prior to reaching the target. The objective of this study was to evaluate qualitatively the essential basic properties of oral solid dosage forms containing 800 mg of mesalamine produced in compounding pharmacies, identified as M1, M2 and M3, comparing them with the following pharmaceutical products: reference medicine (R) and generic (G). Samples were submitted to visual analysis and weight variation and disintegration tests. The results obtained in relation to the visual aspect and the tests related to weight were satisfactory for all the samples. On the other hand, the evaluation of the enteric performance was unsatisfactory for the samples M1 and M2, while the samples M3, R and G were approved in the acid and basic stages of the disintegration test. Thus, it may be inferred that compounding pharmaceutical establishments in Brazil have found difficulties in fulfilling the specifications necessary for mesalamine to reach the colon region, indispensable for its pharmacological effect.

Dental plaque colonized with bacteria can be aspirated from the oropharynx to the lungs, and leads to Ventilator-associated Pneumonia. Proper practice of removal the dental plaque by brushing the teeth using the child toothbrush was shown to be effective in preventing the accumulation of dental plaque. This study aims to determine the current oral care practices in the Intensive Care Unit in two tertiary hospitals in Kelantan. The total of 261 nurses participated in this study. The overall finding from this study showed that only a small proportion of the nurses used the child toothbrush for oral care practice. This study showed there is a need to have a standardized protocol for oral care in the ICUs in order to improve nurses oral care practice

Rabies virus is an important causative agent of disease resulting in an acute infection of the nervous system and death. Although curable if treated in a timely manner, rabies remains a serious public health issue in developing countries, and the indigenous threat of rabies continues in developed countries because of wildlife reservoirs. Control of rabies in wildlife is still an important challenge for governmental authorities.

Reverse vaccinology aims to accelerate subunit vaccine design by rapidly predicting which proteins in a pathogenic bacterial proteome are putative protective antigens. Support vector machine classification is a machine learning approach that has been applied to solve numerous classification problems in biological sciences but has not previously been incorporated into a reverse vaccinology approach. A training data set of 136 bacterial protective antigens paired with 136 non-antigens was constructed and bioinformatic tools were used to annotate this data for predicted protein features, many of which are associated with antigenicity (i.e. extracellular localization, signal peptides and B-cell epitopes). Annotation was used to train support vector machine classifiers that exhibited a maximum accuracy of 92% for discriminating protective antigens from non-antigens as assessed by a leave-tenth-out cross-validation approach. These accuracies were superior to those achieved when annotating training data with auto and cross covariance transformations of z-descriptors for hydrophobicity, molecular size and polarity, or when classification was performed using regression methods. To further validate support vector machine classifiers, they were used to rank all the proteins in six bacterial proteomes for their antigenicity. Protective antigens from the training data were significantly recalled (enriched) in the top 75 ranked proteins for all six proteomes as assessed by a Fisher's exact test (p < 0.05). This paper describes a superior workflow for performing reverse vaccinology studies and provides a benchmark training data set that can be used to evaluate future methodological improvements.► Support vector machine classifiers improve bacterial protective antigen prediction. ► Classifiers significantly recall known antigens in the background of a proteome. ► Subcellular localization and B-cell epitopes correlate with antigenicity.

Photodynamic therapy (PDT) is a promising option in the treatment of cancer. Efficient photosensitizers are available but many of them have insufficient physico-chemical properties for parenteral application. We have established nanoparticles consisting of human serum albumin (HSA) as a drug carrier system for 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrine (mTHPP) and 5,10,15,20tertrakis(m-hydroxyphenyl)chlorin (mTHPC), two well-known photosensitizers.

This work presents the kinetic modelling and simulation of saponification of ethyl acetate in the presence of Sodium hydroxide in a plug flow reactor, Continues stirred tank reactor using Aspen Plus simulation Software. The continuous flow stirred-tank reactor (CSTR), also known as vator back mix reactor, is a common ideal reactor type in chemical engineering. A CSTR often refers to a model used to estimate the key unit operation variables when using a continuous agitated-tank reactor to reach a specified output. Plug flow reactors are widely used in the industry due to the non-mixing property. The use of plug flow reactors becomes significant when there is a need for continuous large scale reaction or fast reaction. Plug flow reactors have a high volumetric unit conversion as the occurrence for side reactions is minimum.

This essue have the aim to put clear the mechanism of the pill. It has an anticonceptive effect, no dooubt, but could it have another effect. Why laboratory din´t explain all the effects of the pill. Have they fear, if yes, for what reason they silenced the abortive effect effects in many cases? We will try to put it as clear as we can.