Development and Evaluation of Microemulsions for Transdermal Delivery of Insulin

Insulin-loaded microemulsions for transdermal delivery were developed using isopropyl myristate or oleic acid as the oil phase, Tween 80 as the surfactant, and isopropyl alcohol as the cosurfactant. The pseudoternary phase diagrams were constructed to determine the composition of microemulsions. The insulin permeation flux of microemulsions containing oleic acid as oil phase through excised mouse skin and goat skin was comparatively greater than that of microemulsions containing isopropyl myristate as oil phase. The insulin-loaded microemulsion containing 10% oleic acid, 38% aqueous phase, and 50% surfactant phase with 2% dimethyl sulfoxide (DMSO) as permeation enhancer showed maximum permeation flux (4.93 ± 0.12 μg/cm2/hour) through goat skin. The in vitro insulin permeation from these microemulsions was found to follow the Korsmeyer-Peppas model (R2 = 0.923 to 0.973) over a period of 24 hours with non-Fickian, “anomalous” mechanism. Together these preliminary data indicate the promise of microemulsions for transdermal delivery of insulin

MODIFICATION OF GUMS BY PERIODATE OXIDATION: A NATURAL CROSS-LINKER

Scientists throughout the world are in search of novel modified biopolymer to fabricate smart drug delivery systems based on hydrogel formulations using several cross-linkers like glutaraldehyde, glyoxal, epichlorhydrin, adipic acid dihydrazide, carbodiimide, genipin, etc. Agents that are fused into the polymeric structure like isocyanates, glutaraldehyde, polyepoxides, etc., and are extremely toxic in nature. In addition, these are susceptible to percolate out into the body on biodegradation of polymeric structure. As an alternative to these toxic cross-linking agents, the periodate-Schiff base staining technique is widely being used for cross-linking in biology and biochemistry. The mechanism of this cross-linking technique is based on the reaction in-between the Schiff reagent and the aldehydes produced via the periodate oxidation. During the past few decades, several researchers have already been studied on the natural gums and also, developed their dialdehyde derivatives via the periodate oxidation technique. These periodate oxidized gums are being used to cross-link gelatin, other proteins and chitosan to develop various smart systems for drug delivery, tissue engineering, wound dressing, edible films, etc. The current review presents a comprehensive discussion of the available reported literature on the periodate oxidation of various gums and their use as natural cross-linker

Solubility and Dissolution Enhancement of Etoricoxib by Solid Dispersion Technique Using Sugar Carriers

The aim of the present study was to improve solubility and dissolution of the poorly aqueous soluble drug, etoricoxib by solvent evaporation technique using various sugar carriers, such as lactose, sucrose, and mannitol. Etoricoxib solid dispersions and their respective physical mixtures using lactose, sucrose, and mannitol were prepared in different ratios by solvent evaporation technique. The percent yield, drug content, saturation solubility, and in vitro dissolution of etoricoxib solid dispersions and physical mixtures were analyzed. Etoricoxib solid dispersions were characterized by FTIR spectroscopy, XRD, and DSC analysis. The FTIR spectroscopic analysis revealed the possibility of intermolecular hydrogen bonding in various solid dispersions. The XRD and DSC studies indicated the transformation of crystalline etoricoxib (in pure drug) to amorphous etoricoxib (in solid dispersions) by the solid dispersion technology. Both the aqueous solubility and dissolution of etoricoxib were observed in all etoricoxib solid dispersions as compared with pure etoricoxib and their physical mixtures. The in vitro dissolution studies exhibited improved dissolution in case of solid dispersion using lactose than the solid dispersions using both sucrose and mannitol. The in vitro dissolution of etoricoxib from these solid dispersions followed Hixson-Crowell model

Antimicrobial activity assessment of time-dependent release bilayer tablets of amoxicillin trihydrate

O objetivo do presente estudo foi avaliar a atividade antimicrobiana de formulações de comprimidos de dupla camada contendo amoxicilina triidratada para liberação tempo dependente e avaliação da liberação in vitro do fármaco pelo ensaio de atividade antimicrobiana utilizando o método de difusão em placa de ágar. Os comprimidos de dupla camada consistem em uma camada para liberação retardada e outra sustentada. O método de compressão direta foi usado para a preparação dos comprimidos de dupla camada contendo Eudragit-L 100 D55 como polímero para liberação retardada e HPMCK4M ou HPMCK15 como polímeros para liberação sustentada. As formulações de comprimidos de dupla camada contendo amoxicilina triidratada foram avaliadas quanto a dureza, espessura, friabilidade, variação de peso e conteúdo de fármaco. Além disso, a liberação do fármaco in vitro foi avaliada por ensaio de atividade antimicrobiana usando S. aureus e E. coli como microrganismos teste. A alíquota das amostras do estudo de liberação do fármaco in vitro demonstrou ser efetiva contra ambos os microrganismos por um período de 16 horas devido à ação sustentada. O estudo de liberação do fármaco in vitro e o ensaio de atividade antimicrobiana mostraram que os comprimidos de dupla camada tiveram um perfil de liberação sustentada do fármaco com um pico de liberação após 2 horas de ensaio. O menor valor de MIC (2 ug/mL) dos comprimidos de dupla camada quando comparados à formulação comercial (5 ug/mL) representa uma boa atividade antimicrobiana.The aim of present study was the assessment of antimicrobial activity of prepared time-dependent release bilayer tablets of amoxicillin trihydrate and in vitro evaluation of drug release by antimicrobial assay using agar plate diffusion method. The bilayer tablets comprised of a delayed and sustained release layer. Direct compression method was used for the preparation of bilayer tablets containing Eudragit-L100 D55 as delayed release polymer, and HPMCK4M and HPMCK15 as sustained release polymers. The prepared bilayer tablets containing amoxicillin trihydrate were evaluated for hardness, thickness, friability, weight variation and drug content. Further, in vitro drug release was assessed by antimicrobial assay using S. aureus and E. coli as test microorganisms. The aliquot samples of in vitro drug release study were found to be effective against both microorganisms for 16 hours due to sustained action. The in vitro drug release study and antimicrobial assay showed that bilayer tablets have sustained release profile of drug delivery with time-dependent burst release after a lag-time of 2 hours. The lower MIC value (2 µg/mL) of prepared bilayer tablets vis-à-vis marketed preparation (5 µg/mL) represented its good antimicrobial activity

A COMPARATIVE STUDY OF STEREOCHEMICAL EFFECTS OF ANTI-PROSTATE AGENTS BY MOLECULAR DOCKING

Objective: A comparative study of anti-prostate agents to investigate the stereochemical influences on binding affinity by molecular docking.Methods: Structures of enantiomers (R and S stereoisomers) for known anti-prostate cancer (PCa) agents were drawn using ChemBioDraw 2D software. Thereafter, they were converted to 3D structures using the ChemBioDraw 3D software in which they were subjected to energy minimization using the MM2 method and then saved as PDB extension files which can be accessed using the ADT interface. AutoDock Vina (ADT) 1.5.6 software version was used for molecular docking study.Results: A total of 12 different anti-PCa agents were selected and drawn including well-known drug R-bicalutamide. All molecules showed the binding affinity with respect to the nature of stereochemistry. R-stereoisomers showed better interaction as well as binding affinity toward 1z95 (mutated androgen receptor protein involved in the progression of PCa) whereas their S-stereoisomers were found inferior in comparison.Conclusion: This study showed that CB1-R and R-bicalutamide (with R-stereochemistry) were better in binding affinity comparative to their counterpart CB1-S and S-Bicalutamide (with S-stereochemistry). All the selected anti-PCa agents were showing the effect of stereochemical center; therefore, we must choose the right kind of stereochemistry while planning to develop the newer anti-PCa agents

Spin order dependent skyrmion stabilization in MnFeCoGe hexagonal magnets

Topological magnetic skyrmions in centrosymmetric systems exhibit a higher degrees of freedom in their helicity, hence possess a great potential in the advanced spintronics including skyrmion based quantum computation. However, the centrosymmetric magnets also display non-topological trivial bubbles along with the topological skyrmions. Hence it is utmost priority to investigate the impact of different magnetic ground states and their underlying interactions on the stabilization of magnetic skyrmions in cetrosymmetric magnets. Here, we present a combined theoretical and experimental study on the role of non-collinear magnetic ground state on the skyrmion stabilization in a series of exchange frustrated non-collinear ferromagnetic system MnFe1-xCoxGe. With the help of neutron diffraction (ND) and Lorentz transmission electron microscopy (LTEM) studies, we show that hexagonal skyrmions lattice emerges as a stable field driven state only when the underlying magnetic ground state is collinear with easy-axis anisotropy. In contrast, non-topological type-II bubbles are found to be stable state in the case of non-collinear magnetic ordering with partial in-plane anisotropy. Furthermore, we also find that the skyrmions transform to the non-topological bubbles when the system undergoes a spin reorientation transition from the easy-axis to easy-cone ferromagnetic phase. Our results categorically establish the significant role of in-plane magnetic moment/anisotropy that hinders the stability of skyrmion both in the case of collinear and non-collinear magnets. Thus, the present study offers a wide range of opportunities to manipulate the stability of dipolar skyrmions by changing the intrinsic characteristics of the materials.Comment: 18 pages, 4 figure