An overview: Matrix tablets as sustained release.

Oral route is the most preferred route for administration of drugs. Tablets are the most popular oral formulation available in the market and preferred by the patients and physician alike. In long-term therapy for the treatment of chronic disease conditions, conventional formulations are required to be administered multiple doses and therefore have several disadvantages. The primary benefit of a sustained release dosage form compared to a conventional dosage form, is the uniform drug plasma concentration and therefore uniform therapeutic effect. Matrix system are favored because of their simplicity, patient compliance etc, than traditional drug delivery which have many drawbacks like repeated administration, fluctuation in blood concentration level etc. Introduction of Matrix tablet as Sustained release has given a new break through for novel drug delivery system (NDDS) in the field of Pharmaceutical technology. Matrix systems are widely used for the purpose of sustained release. It is the release system which prolongs and controlls the release of drug that is dissolved or dispersed. In fact, a matrix is defined as a well-mixed composite of one or more drugs with gelling agent i.e. hydrophilic polymers. By the sustained release method therapeutically effective concentration can be achieved in the systemic circulation over an extended period of time, thus achieving better compliance of patients. Numerous sustained release oral dosage forms such as membrane controlled system, matrices with water soluble/insoluble polymers or waxes and osmotic systems have been developed, intense research has been recently focused on the designed of sustained release systems for poorly water soluble drugs

DESIGN AND EVALUATION OF FAST DISSOLVING TABLETS OF ERGOTAMINE TARTARATE

Objective: The main objective of this study was to formulate and evaluate the fast dissolving tablets of ergotamine tartarate with synthetic superdisintegrants. Methods: Various formulations were prepared by direct compression method using different concentrations of crospovidone (12.5%-62.5%) and croscarmallose sodium (12.5%-62.5%) as superdisintegrants. Formulations were evaluated for precompressional parameters and postcompressional parameters like uniformity of weight, thickness, hardness, friability, drug content, wetting time, the water absorption ratio, in vitro disintegration time and in vitro dissolution study. Results: Results revealed that among the 10 formulations, the formulation F5 containing 62.5% of crospovidone and formulation F10 containing 62.5% of croscarmallose sodium was found to be promising formulations. F5 shown disintegration time of 12 seconds and the drug release was up to 96% in 30 minutes and F10 shown disintegration time of 18 seconds and the drug release was up to 89% in 30 minutes. Conclusion: From the result obtained, it can be concluded that formulation of fast dissolving tablet using crospovidone as a superdisintegrant showed improved disintegration and solubility and hence better patient complianc

A Validated RP-HPLC Method for the Estimation of Pizotifen in Pharmaceutical Dosage Form

A simple, selective, linear, precise, and accurate RP-HPLC method was developed and validated for rapid assay of Pizotifen in pharmaceutical dosage form. Isocratic elution at a flow rate of 1.0 mL/min was employed on Chromosil C18 (250 mm × 4.6 mm, 5 μm) column at ambient temperature. The mobile phase consists of methanol : acetonitrile in the ratio of 10 : 90 v/v. The UV detection wavelength was 230 nm, and 20 μL sample was injected. The retention time for Pizotifen was 2.019 min. The percent RSD for accuracy of the method was found to be 0.2603%. The method was validated as per the ICH guidelines. The method can be successfully applied for routine analysis of Pizotifen in the rapid and reliable determination of Pizotifen in pharmaceutical dosage form

Genetic characterization of Indian type O FMD virus 3A region in context with host cell preference

The 3A region of foot-and-mouth disease virus has been implicated in host range and virulence. For example, amino acid deletions in the porcinophilic strain (O/TAW/97) at 93-102 aa of the 153 codons long 3A protein have been recognized as the determinant of species specificity. In the present study, 18 type O FMDV isolates from India were adapted in different cell culture systems and the 3A sequence was analyzed. These isolates had complete 3A coding sequence (153 aa) and did not exhibit growth restriction in cells based on species of origin. The 3A region was found to be highly conserved at N-terminal half (1-75 aa) but exhibited variability or substitutions towards C-terminal region (80-153). Moreover the amino acid substitutions were more frequent in recent Indian buffalo isolates but none of the Indian isolates showed deletion in 3A protein, which may be the reason for the absence of host specificity in vitro. Further inclusive analysis of 3A region will reveal interesting facts about the variability of FMD virus 3A region in an endemic environment

Fast Dissolving Tablets of Fexofenadine HCl by Effervescent Method

In the present work, fast dissolving tablets of fexofenadine HCl were prepared by effervescent method with a view to enhance patient compliance. Three super-disintegrants viz., crospovidone, croscarmellose sodium and sodium starch glycolate along with sodium bicarbonate and anhydrous citric acid in different ratios were used and directly compressible mannitol (Pearlitol SD 200) to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity and in vitro dispersion time. Based on the in vitro dispersion time (approximately 20 s), three formulations were tested for in vitro drug release pattern in pH 6.8 phosphate buffer, short-term stability at 40°/75% RH for 3 mo and drug-excipient interaction (IR spectroscopy). Among the three promising formulations, the formulation ECP3 containing 8% w/w of crospovidone and mixture of 24% w/w sodium bicarbonate 18% w/w of anhydrous citric acid emerged as the best (t50% 4 min) based on the in vitro drug release characteristics compared to conventional commercial tablet formulation (t50% 15 min). Short-term stability studies on the formulations indicated that there are no significant changes in drug content and in vitro dispersion time (P<0.05)

Molecular Epidemiology of Rabies Virus Isolates in India

In India, rabies is enzootic and is a serious public health and economic problem. India has a large population of stray dogs which, together with a lack of effective control strategies, might have led to the persistence of rabies virus (RV) in the canine population. Our objective was to study the molecular epidemiology of RV isolates in India based on nucleotide sequence analysis of 29 RV isolates originating from different species of animals in four states. Here we have analyzed two sets of sequence data based upon a 132-nucleotide region of the cytoplasmic domain (CD) of the G gene (G-CD) and a 549-nucleotide region (Psi-L) that combines the noncoding G-L intergenic region (Psi) and a fragment of the polymerase gene (L). Phylogenetic analysis revealed that the RV isolates belong to genotype 1 and that they were related geographically but were not related according to host species. Five different genetic clusters distributed among three geographical regions were identified. Comparison of the deduced amino acid sequences of G-CD between RV isolates revealed three amino acid changes (amino acid 462G [aa462G], aa465H, and aa468K) that distinguished the Indian RVs from RV isolates in other parts of the world. Analysis of the data indicated that the dog rabies virus variants are the major circulating viruses in India that transmit the disease to other domestic animals and humans as well

Serological Hendra Virus Diagnostics Using an Indirect ELISA-Based DIVA Approach with Recombinant Hendra G and N Proteins

Since the identification of Hendra virus (HeV) infections in horses in Australia in 1994, more than 80 outbreaks in horses have been reported, and four out of seven spillover infections in humans had a fatal outcome. With the availability of a subunit vaccine based on the HeV-Glycoprotein (HeV-G), there is a need to serologically Differentiate the Infected from the Vaccinated Animals (DIVA). We developed an indirect ELISA using HeV-G expressed in Leishmania tarentolae and HeV-Nucleoprotein (HeV-N) expressed in recombinant baculovirus-infected insect cells as antigens. During evaluation, we tested panels of sera from naïve, vaccinated and infected horses that either originated from a Hendra-virus free region, or had been pre-tested in validated diagnostic tests. Our data confirm the reliability of this approach, as HeV-N-specific antibodies were only detected in sera from infected horses, while HeV-G-specific antibodies were detected in infected and vaccinated horses with a high level of specificity and sensitivity. Given the excellent correlation of data obtained for German and Australian HeV-negative horses, we assume that this test can be applied for the testing of horse serum samples from a variety of geographical regions

Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We previously developed highly thermo-tolerant monomeric and trimeric receptor-binding domain derivatives that can withstand 100 °C for 90 min and 37 °C for four weeks and help eliminate cold-chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations and a 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for upcoming Phase I human clinical trials and that there is potential for increasing the efficacy with vaccine matching to improve the responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions, which show that, while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain

Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We previously developed highly thermo-tolerant monomeric and trimeric receptor-binding domain derivatives that can withstand 100 &deg;C for 90 min and 37 &deg;C for four weeks and help eliminate cold-chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations and a 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for upcoming Phase I human clinical trials and that there is potential for increasing the efficacy with vaccine matching to improve the responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions, which show that, while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain