PROCESS AND PARAMETERS AFFECTING DRUG RELEASE PERFORMANCE OF PREPARED CROSS-LINKED ALGINATE HYDROGEL BEADS FOR EZETIMIBE

Objective: The objective of this study was to formulate an oral sustained release delivery system of ezetimibe mucoadhesive beads by ionic gelation technique based on sodium alginate used as a hydrophilic carrier in combination with carbopol 934P which acts as a rate modifier.Methods: Microbeads of ezetimibe were prepared using an easy method of ionotropic gelation by little modification while in addition of drug. The prepared beads were characterised for mean particle size, entrapment efficiency, swelling capacity, and in vitro release. They were also subjected to various studies such as Fourier Transform Infrared Spectrophotometer (FTIR) Spectroscopy for drug polymer reaction, Scanning Electron Microscopy for surface morphology, and Differential Scanning Calorimetric Analysis to determine the physical state of the drug in the beads.Results: The microspheres of ezetimibe were formulated successfully. The addition of drug concentration gives higher drug loading and higher conc. of Alcl+3 yields small diameter beads and lower drug entrapment. Analysis of the release profiles showed that the data corresponds to zero order release and the diffusion-controlled mechanism as suggested by Higuchi concept.Conclusion: It can be concluded that beads produced by the sequential method had higher drug entrapment. Beads produced by simultaneous yields larger beads in diameter. The concept was cleared that drug release was dependent upon the quantity of polymer and increase in conc. of. aluminium chloride retarded the drug release in the sequential method. Prepared beads enhance the dissolution of ezetimibe and the oral bioavailability and also reduce the fluctuations in the oral bioavailability

THE ROLE OF NEEDLE IN FORMULATION OF pH SENSITIVE SWELLABLE MICROBEADS PREPARED WITH HYDROPHILIC POLYMERS FOR ATORVASTATIN AND THEIR CHARACTERIZATION STUDIES

Objective: The aim of the study was to develop and characterize mucoadhesive microbeads for oral sustained release of atorvastatin by using hydrophilic polymers and application of different process variables in designing of pH sensitive swellable microbeads.Methods: Microbeads were prepared by ionic gelation method. The compatibility studies of atorvastatin with polymers were investigated by differential scanning calorimeter and fourier transform infrared spectroscopy studies. In this work process variable like optimization of curing agents and their quantity, effect of rpm, and their influence in drug entrapment were studied. Prepared beads were characterized for particle size, swelling index, erosion studies and drug release studies.Results: Mixture of alginate and carbopol 934 P at 3.3 % w/v shows sustained release and good mucoadhesive capacity. Furthermore, drug loading and swelling increased with the use of a combination of polymers. On basis of in vitro release studies and swelling studies, it was observed that sodium alginate coated with carbopol 934 P showed sustained release of 84.5 % at end of 10 h in 6.8 phosphate buffer. The optimised batch followed peppas and higuchi release mechanism and releasing the drug by non-fickian transport.Conclusion: The alginate beads with a combination of carbopol 934P showed a sustain release pattern. The release rate and swelling of atorvastatin beads could be adjusted by adding other hydrophilic polymers or by optimising curing agents, curing time and their volume. The zero order of drug release was confirmed for all the batches. The in vitro data was better fit to Higuchi's diffusion model and diffusion rate limited

Formulation studies on cyclodextrin complexes of Meloxicam

ABSTRACT β-Cyclodextrin (β-CD) and HP-β-Cyclodextrin (HP-β-CD) inclusion complexes of piroxicam (PRX) exhibited higher dissolution rates and dissolution efficiency values than the corresponding un-complexed drug. The feasibility of formulating the β-cyclodextrin and HP-β-cyclodextrin complexes of piroxicam (1:3) into tablet dosage forms is evaluated. Solid inclusion complexes of piroxicam prepared by kneading method were formulated into tablets by wet granulation and direct compression methods. All the tablets formulated employing β-cyclodextrin and HP-β-cyclodextrin complexes of piroxicam gave rapid and higher dissolution rates of when compared to that of piroxicam plain tablets. All the prepared tablets fulfilled the official (I.P.) disintegration time specification of uncoated tablets. Overall, tablets prepared by direct compression method disintegrate rapidly when compared to those prepared by wet granulation method. Analysis of dissolution data as per zero-order and first -order kinetic models indicated that the dissolution of piroxicam from all the tablets followed first-order kinetics. In both direct compression and wet granulation methods, tablets formulated employing cyclodextrin complexes (PRXT2, PRXT3, PRXT5, PRXT6) gave higher rates of dissolution (K 1 ) and dissolution efficiency (DE 30 ) values when compared to the corresponding tablets formulated with piroxicam as such (PRXT1, PRXT4). Among all the piroxicam tablets formulated, formulation PRXT2, which is based on PRX-βCD (1:3) kneaded complex, gave highest dissolution. A 17.0 fold increase in the dissolution rate of piroxicam was observed with PRXT2 when compared to its plain tablets ( PRXT1)

Ab initio and DFT studies on structure, vibrational spectra of 4-tert-butyl-1,3-thiazol-2-amine (BTA)

Theoretical studies have been carried out on 4-tert-butyl-1, 3-thiazol-2-amine (BTA) using both the B3LYP/6-311+G and HF/6-311+G methods. The geometrical parameters and vibrational spectra of BTA have been calculated and analyzed. The calculated IR wavenumbers have been compared with the observed FTIR wavenumbers. The complete assignments have been performed based on the potential energy distribution (PED) of the vibrational modes. The wavenumbers obtained from B3LYP method are in good agreement with the observed wavenumbers when compared to HF method. It has been found that there is an excellent correlation with 0.999 regression coefficient between the experiment and calculated vibrations. Thermal properties like rotational constants, zero point vibrational energies and nonlinear optical properties like dipole moment, hyperpolarizabilities, NBO analysis and the effect of temperature on various thermodynamic properties have been calculated and orted

DEVELOPMENT AND CHARACTERIZATION OF GASTRO RETENTIVE MUCOADHESIVE MICROBEADS CONTAINING SIMVASTATIN WITH DIFFERENT CROSS LINKING AGENTS

Objective: The aim of the present work was to prepare and examine drug release of the oral controlled release microbeads using different curing agents by emulsification internal ionic gelation technique. Methods: Cross-linked alginate microbeads were prepared with different cross linking agents by using mucoadhesive properties. The formation and compatibility of microbeads were confirmed by compatibility studies. Prepared microbeads evaluated for encapsulated efficiency, micromeritic properties, drug loading, in vitro wash off studies, in vitro dissolution studies, drug release kinetics and stability studies Results: The in vitro drug release was influenced by both type of curing agents and type of polymers and no significant changes in characterization parameters was observed after 3 mo stability studies. The sustained release profile of optimized batch was found to be 99.66±0.18% in comparison to pure drug profile of 28.64±0.02% at 12 h release study. Results of both wash-off and in vitro studies suggests that batch (SF2) prepared with aluminium chloride has shown better mucoadhesive property. Drug release of optimized batch follows zero order with non fickian mechanism according to Korsmeyer-Peppas equation. Conclusion: The data suggest the use of simvastatin mucoadhesive cross linked microbeads to offer the potential for oral controlled drug delivery with improved gastric retention and capable to provide sustained drug release by using cross linking agents

Registration of ICGV 86031 Peanut Germplasm

ICGV 86031 (Reg. no. GP-58, PI no. 561917) is a spanishtype peanut (Arachis hypogaea L. subsp. fastigiata Waldron var. vulgaris Hartz) developed at the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Patancheru, India. It was released in 1991 by the Plant Materials Identification Committee of ICRISAT because of its resistance to thrips (Thripspalmi Karny), jassid (Empoasca kerri Pruthi), spodoptera [Spodoptera litura (Fabricius)], groundnut leaf miner (Aproaerema modicella Deventer) and bud necrosis virus (BNV), which causes bud necrosis disease (END) in peanut. ICGV 86031 has also been found to be photoperiod insensitive and resistant to iron deficiency chlorosis (4)

The Stress-Response Factor SigH Modulates the Interaction between Mycobacterium tuberculosis and Host Phagocytes

The Mycobacterium tuberculosis stress response factor SigH plays a crucial role in modulating the pathogen's response to heat, oxidative-stress, envelope damage and hypoxia. We hypothesized that the lack of this key stress response factor would alter the interaction between the pathogen and its host cells. We compared the interaction of Mtb, Mtb:Δ-sigH and a strain where the mutation had been genetically complemented (Mtb: Δ-sigH:CO) with primary rhesus macaque bone marrow derived macrophages (Rh-BMDMs). The expression of numerous inducible and homeostatic (CCL) β-chemokines and several apoptotic markers was induced to higher levels in the cells infected with Mtb:Δ-sigH, relative to Mtb or the complemented strain. The differential expression of these genes manifested into functional differences in chemotaxis and apoptosis in cells infected with these two strains. The mutant strain also exhibited reduced late-stage survival in Rh-BMDMs. We hypothesize that the product of one or more SigH-dependent genes may modulate the innate interaction of Mtb with host cells, effectively reducing the chemokine-mediated recruitment of immune effector cells, apoptosis of infected monocytes and enhancing the long-term survival and replication of the pathogen in this milieu The significantly higher induction of Prostaglandin Synthetase 2 (PTGS2 or COX2) in Rh-BMDMs infected with Mtb relative to Mtb: Δ-sigH may explain reduced apoptosis in Mtb-infected cells, as PTGS2 is known to inhibit p53-dependent apoptosis.The SigH-regulon modulates the innate interaction of Mtb with host phagocytes, perhaps as part of a strategy to limit its clearance and prolong its survival. The SigH regulon appears to be required to modulate innate immune responses directed against Mtb

NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection

In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice. Levels of IL-6 also increased. Anti-IL-6 monoclonal antibody treatment of Mtb-infected acute- and chronic-T2DM mice increased survival (to 100%) and reduced pro- and anti-inflammatory cytokine expression. CD11c+ cells were the major source of IL-6 in Mtb-infected T2DM mice. Pulmonary natural killer (NK) cells in Mtb-infected T2DM mice further increased IL-6 production by autologous CD11c+ cells through their activating receptors. Anti-NK1.1 antibody treatment of Mtb-infected acute-T2DM mice increased survival and reduced pro- and anti-inflammatory cytokine expression. Furthermore, IL-6 increased inflammatory cytokine production by T lymphocytes in pulmonary tuberculosis patients with T2DM. Overall, the results suggest that NK-CD11c+ cell interactions increase IL-6 production, which in turn drives the pathological immune response and mortality associated with Mtb infection in diabetic mice

Formulation studies on solid dispersions of celecoxib in superdisintegrants alone and with

ABSTRACT The feasibility of formulating the solid dispersions of celecoxib into tablet dosage forms is evaluated. All the tablets formulated employing solid dispersions of celecoxib in superdisintegrants gave rapid and higher dissolution of celecoxib when compared to that of celecoxib plain tablets. The increasing order of dissolution rate of formulated tablets with various carriers was Croscarmellose (CC)>Pregelatinised starch (PGS)> Primojel(PJ)> Crospovidone (CP). The same order of performance was observed in both the series of tablets formulated employing superdisintegrants alone and in combination with PVP. A 10.80 fold increase in the dissolution rate of celecoxib was observed with tablets formulated employing its solid dispersions in CC (CF4) when compared to plain tablets (CF1). A 15.24 fold increase in the dissolution rate of celecoxib was observed with tablets formulated employing its solid dispersions in combined carriers CC and PVP (CF8) when compared to its plain tablets (CF1)

REGULATORY REASONS BEHIND THE BAN OF VARIOUS IRRATIONAL FIXED DOSE COMBINENT DRUGS

<p><i>Medicines are an integral part of healthcare. More than one drug is frequently used for treatment of either single ailment or multiple comorbid conditions. Sometimes, two or more drugs are combined in a fixed ratio into a single dosage form, which is termed as fixed dose combinations (FDCs). The FDCs are justified when they demonstrate clear benefits in terms of (a) potentiating the therapeutic efficacy, (b) reducing the incidence of adverse effect of drugs, (c) having pharmacokinetic advantage, (d) better compliance by reducing the pill burden, (e) reducing dose of individual drugs, (f) decreasing development of resistance, and (g) cheaper than individual drug because of reduced cost from packaging to distribution. It is important that the above claims are adequately supported by scientific evidence.</i></p><p><strong>Keywords:</strong>  <i>Fixed Dose Combinations, Regulatory Reasons.</i></p&gt