Formulation of Extended-Release Metformin Hydrochloride Matrix Tablets

Purpose: To develop and characterize an oral extended-release matrix tablet of metformin hydrochloride using a combination of a hydrophobic carrier and a hydrophilic polymer, and two types of formulation techniques.Methods: Various metformin hydrochloride formulations containing a hydrophobic carrier (stearic acid) and a hydrophilic polymer (polyethylene oxide) were prepared using a 32 factorial design. Two types of formulation techniques – melt granulation and direct compression – were evaluated. The influence of the carrier, polymer and preparation method on metformin release from the formulations in vitro as well as other physicochemical properties were studied. The release data were subjected to various release kinetic models and also compared with those of a commercial brand.Results: The physicochemical characteristics of all the granules and tablets were generally satisfactory. Optimization results indicate that the release rate of metformin HCl was directly proportional to the levels of stearic acid (SA) and polyethylene oxide (PEO) in the tablet formulations. Release rate was also dependent on the method of granulation used. Kinetic analysis showed that the formulation containing 30 %w/w of polymer exhibited release similar to that of the commercial brand with a similarity factor (f2) of 81.1. Melt granulation was more effective in extending drug release than direct compression. Release mechanism followed most closely the Korsemeyer-Peppas model with a correlation coefficient (r2) and 0.991.Conclusion: The use of a hydrophobic carrier along with a hydrophilic polymer effectively controls the initial rapid release of a highly water soluble drug such as metformin HCl. Hot melt granulation method was especially more effective in achieving this than the direct compression method.Keywords: Metformin hydrochloride, Matrix tablets, Polyethylene oxide, Stearic acid, Hot melt granulation, In vitro release

Production of Antibiotics from Soil-Isolated Actinomycetes and Evaluation of their Antimicrobial Activities

Purpose: To investigate the production of antibiotic from actinomycetes isolated from soil and evaluate its antimicrobial activities. Methods: In a medium formulation study, A-4 and A-4 actinomycete mutant strains (out of the six strains selected from the nine actinomycetes that were screened) were evaluated for maximum antibiotic production using various carbon and nitrogen sources. Zone of inhibition and packed cellvolume were the parameters used for the evaluation. Various fermentation conditions such as pH, temperature and dissolved oxygen were also optimized for maximal production of antibiotic from both A-4 and A-4 mutant. Results: Some actinomycetes strains showed promising antimicrobial activity against different strains of bacteria and fungi. Out of the six strains selected, one strain, designated A-4, showed maximum antimicrobial property against Gram positive and Gram negative strains as well as against various fungi. Conclusion: Findings from this investigation reveal that strain A-4 and A-4 mutant strains, in that order, exhibited superior antimicrobial activities to other soil isolates of actinomycetes.Keywords:  Actinomycete, Antibiotic, MIC, fermentation

PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES EFFECT OF SESBANIA GRANDIFLORA AND SESBANIA SESBAN BARK ON CARRAGEENAN INDUCED ACUTE INFLAMMATION AND ADJUVANT-INDUCED ARTHRITIS IN RATS

ABSTRACT Nitric Oxide (NO) can autoregulate its own formation by feedback inhibition of the inducible Nitric Oxide Synthase (iNOS). Modulation of biosynthesis or activity of NO results in amelioration if pathogenesis of experimental arthritis. However, little is known about feedback mechanism on NO generation in response to carrageenan induced paw oedema and adjuvant-induced arthritis. In the present study we have examined the effects of prophylactic administration of extracts of bark of Sesbania grandiflora and Sesbania sesban on the development of carrageenan induced paw oedema and adjuvant -induced arthritis to assess influence of high NO level in the form of exogenous herbal extracts of bark of Sesbania grandiflora and Sesbania sesban in the progress of inflammation. Inflammation was assessed by measuring paw swelling. Increased paw oedema of the injected paw measured on 1 st to 12 th hrs which is feature of carrageenan induced inflammation was significantly reduced after prophylactic administration of petroleum ether, chloroform and methanol extracts of bark of Sesbania grandiflora (300mg/kg b.w. p.o.) and Sesbania sesban (300mg/kg b.w. p.o.) and arthritis was assessed by measuring primary and secondary paw swelling and changes in thymus, spleen and body weight. Increased swelling of the non injected paw (secondary paw) measured on days 14 and 21, injected paw swelling (primary paw) measured on days 3, 14 and 21, spleenomegaly, thymic involutions and loss in body wt. which are features of adjuvant-induced arthritis were effectively reduced after prophylactic administration of extracts of bark of Sesbania grandiflora and Sesbania sesban . These data suggests that high NO level in the from extracts of Sesbania grandiflora and Sesbania sesban may suppress initial stages of immune response to carrageenan and adjuvant injection probably by inhibiting iNOS expression through feedback inhibition mechanism. However, further studies are required to unravel the mechanism involved in these effects of extracts of bark of Sesbania grandiflora and Sesbania sesban and their clinical implications

Preparation, characterization and in-vitro efficacy of quercetin loaded liquid crystalline nanoparticles for the treatment of asthma

© 2019 Elsevier B.V. The present study aims to formulate quercetin loaded liquid crystalline nanoparticles (LCN) and surface modified liquid crystalline nanoparticles (sm-LCN) as well as investigate their anti-inflammatory activity in human primary bronchial epithelial cell line (BCi-NS1.1) induced with lipopolysaccharide (LPS). Quercetin LCN were prepared using ultrasonication method. The formulated LCNs and sm-LCNs were characterised in terms of particle size, zeta potential as well as the drug encapsulation efficiency. Furthermore, their morphology and in vitro release profile were also studied. In addition, the anti-inflammatory activity of quercetin LCN and sm-LCNs were evaluated by measuring the concentration of pro-inflammatory markers namely interleukin (IL)-1β, IL-6 and IL-8 in BCI-NS1.1 cell lines via cytometric bead array. The molecular mechanism inherent to the inclusion of quercetin into monoolein nanosystem and surface modification of the nanosystem with chitosan was elucidated via molecular mechanics simulations. Quercetin LCN and sm-LCN significantly (p < 0.05) decreased the production of IL-1β, IL-6 and IL-8 compared to LPS only group. Encapsulation of quercetin into LCN and sm-LCN further enhanced its anti-inflammatory activity compared to quercetin in dimethyl sulfoxide (DMSO). In addition to that, quercetin LCN and sm-LCN also exhibited comparable activity to fluticasone in terms of significantly (p < 0.05) reducing the production of IL-1β and IL-6. Quercetin loaded LCN and sm-LCN could be a potential therapeutic intervention for asthma as they are efficacious in suppressing the production of key pro-inflammatory cytokines associated with the development of asthma

Folate‐targeted nanoparticles show efficacy in the treatment of inflammatory arthritis

Objective To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 [G5]) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and to investigate the activity of an FA‐ and methotrexate (MTX)–conjugated dendrimer (G5‐FA‐MTX) as a therapeutic for the inflammatory disease of arthritis. Methods In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescence‐tagged G5‐FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen‐induced arthritis to evaluate the therapeutic potential of G5‐FA‐MTX. Results Folate‐targeted dendrimer bound and internalized in a receptor‐specific manner into both folate receptor β–expressing macrophage cell lines and primary mouse macrophages. The conjugate G5‐FA‐MTX acted as a potent antiinflammatory agent and reduced arthritis‐induced parameters of inflammation such as ankle swelling, paw volume, cartilage damage, bone resorption, and body weight decrease. Conclusion The use of folate‐targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for antiinflammatory therapy in rheumatoid arthritis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86938/1/30459_ftp.pd

Structure Activity Relationship of Dendrimer Microbicides with Dual Action Antiviral Activity

Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published.Dendrimers with optimized activity against HIV-1 and HSV-2 were identified with respect to the number of lysine branches (generations) and surface groups. Antiviral activity was determined in cell culture assays. Time-of-addition assays were performed to determine dendrimer mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene disulfonic acid (DNAA) and 3,5-disulfobenzoic acid exhibiting the greatest anionic charge and hydrophobicity of the seven surface groups tested. Their anti-HIV-1 activity did not appreciably increase beyond a second-generation dendrimer while dendrimers larger than two generations were required for potent anti-HSV-2 activity. Second (SPL7115) and fourth generation (SPL7013) DNAA dendrimers demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and SPL7115 inhibited viral entry with similar potency against CXCR4-(X4) and CCR5-using (R5) HIV-1 strains. SPL7013 was not toxic and provided at least 12 h protection against HSV-2 in the mouse vagina.Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is formulated as VivaGel(R) and is currently in clinical development to provide protection against HIV and HSV. SPL7013 could also be combined with other microbicides