Electrospinning of ampicillin trihydrate loaded PLA nanofibers: effect of drug concentration and PLGA addition on its morphology, drug delivery and mechanical properties

The aim of the study is to produce ampicillin trihydrate loaded PLA and PLA/PLGA polymeric nanofibers using HFIP as solvent via electrospinning. The effect of ampicillin trihydrate concentration (4-12%), the addition of PLGA and the amount of added PLGA (20-80%) on the spinnability of the solutions and morphology, average nanofiber diameter, encapsulation efficiency, in vitro drug release and mechanical properties of PLA and PLA/PLGA nanofibers were examined. All nanofibers have shown to have favorable encapsulation efficiency and mechanical properties. As the amount of ampicillin trihydrate increased and PLGA was added, nanofiber diameter increased while mechanical properties decreased. However, as the amount of added PLGA increased, a decrease in nanofiber diameter was observed. The increase in the drug amount caused an increase in the burst effect. The ideal drug concentration was determined to be 8% (F2), as it allows the prolonged and controlled drug release for up to 10 days. While in vitro drug release decreased with the addition of PLGA to PLA, it increased with the increasement of added PLGA to PLA. As a result of the study, it was concluded that the amount of the drug and the added PLGA concentration may affect the average nanofiber diameter, morphology, in vitro drug release and mechanical properties of the obtained electrospun PLA nanofibers.

Chitosan-based nanoparticles sustenance and potentiation of the antibacterial effect of ampicillin against drug resistance among strains of Escherichia coli

The study seeks to evaluate nanoparticles based on chitosan for enhanced delivery of ampicillin in plasmid-mediated drug resistance. Serial dilutions of a mixed population of E. coli was plated on nutrient agar and streaked on Replica-plate 25 random colonies using MacConkey agar with or without ampicillin (100 µg/ml) daily for 96 h. Nanoparticles were prepared by cross-linking chitosan with sodium tripolyphosphate with ampicillin trihydrate adsorbed. Three different batches were prepared for optimization. The nanoparticles were optimized based on encapsulation efficiency, in vitro drug release, pH stability and microbiological assay using two laboratory strains of E. coli. Increased resistance to ampicillin due to possible plasmid transfer was established in vitro after 96 h. The encapsulation efficiency of the three batches was between 21-57 %. The drug release showed a burst effect and slow extended release over 8 h and reached a peak of about 19 % release at the 6 and 7 h in Batch A, B and C. The pH of the particles was stable over a period of 6 d. The nanoparticles containing only 0.075 mg of ampicillin dropped in an agar well plate inoculated with 1 ml of E. coli J62 lac pro trp hispFlac::Tn3 (AmpR) gave an IZD of ≥ 25 mm. Chitosan nanoparticles holds good potentials in potentiating the antibacterial effect of ampicillin against possible plasmid-mediated drug resistance

Direct Observation of Growth Rate Dispersion in the Enzymatic Reactive Crystallization of Ampicillin

Prediction and control of crystal size distributions, a prerequisite for production of consistent crystalline material in the pharmaceutical industry, requires knowledge of potential non-idealities of crystal growth. Ampicillin is one such medicine consumed in crystal form (ampicillin trihydrate). Typically it is assumed that all crystals of the same chemical and geometric type grow at the same rate, however a distribution of growth rates is often observed experimentally. In this study, ampicillin produced enzymatically is crystallized and a distribution of growth rates is observed as individual crystals are monitored by microscopy. Most studies of growth rate dispersion use complex flow apparatuses to maintain a constant supersaturation or imprecise measurements of size distributions to reconstruct growth rate dispersions. In this study, the controllable enzyme reaction enables the same information to be gathered from fewer, less complicated experiments. The growth rates of individual ampicillin trihydrate crystals were found to be normally distributed, with each crystal having an intrinsic growth rate that is constant in time. Differences in the individual crystals, such as different number and arrangement of dislocations and surface morphology, best explain the observed growth rates. There is a critical supersaturation below which growth is not observed, thought to be caused by reactants adsorbing to the crystal surface and pinning advancing growth steps. The distribution of critical supersaturation also suggests that individual crystals’ surface morphologies cause a distribution of growth rates.

Facile Synthesis, Characterization of New Quinazolinones with Different Azo Compounds, 1,2,3-Triazole Moieties and Evaluation Their Anti-bacterial Activity.

In the present research, a series of some azo compounds (5-9) and 1,2,3-triazoles derived from 2-methyl quinazolin-4(3H)-one were synthesized successfully by stepwise routes includes the following: 3-amino-2-methylquinazolin-4(3H)-one (3) prepared firstly by conversion of 2-aminobenzoic acid into methyl 2-aminobenzoate (1) followed by reaction with acetic anhydride to form methyl -2-acetamidobenzoate (2). The amide then allowed reacting with hydrazine hydrate to give compound (3). Diazotization reaction with sodium nitrite in the presence of hydrochloric acid yield the 3-(chlorodiazenyl)-2-methylquinazolin-4(3H)-one(4). Diazonium salt (4) then enter two different routes. The first route was its conversion into azo compounds (5-9) by reaction with coupling components.The second route included formation of 1,2,3- triazole derivatives by interconversion of compound (4) into azido compound (10) followed by treatment with ethyl acetoacetate, acetyl acetone to give 5-methyl-1-(2-methyl-4-oxoquinazolin-3(4H)-yl)-1H-1,2,3-triazole-4-carboxylic acid (11) and 3-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)-2-methylquinazolin-4(3H)-one (12) in good yield. Newly synthesized derivatives were characterized spectroscopically by FTIR, 13C-NMR and 1H-NMR spectral technique and by determination of their physical properties. Also end time of reactions monitored by thin layer chromatography. The antibacterial potential of synthesized azo compounds, 1,2,3-triazole of methyl quinazolin-4(3H)-one has been tested against the growth of four gram positive and gram negative pathogenic bacterial strains using agar well diffusion method. Ampicillin trihydrate used as reference drug. The results of the antibacterial study showed that compounds (7-9) appeared good activity.

Synthesis and characterization of novel dimerics-triazine derivatives as potential anti-bacterial agents against MDR clinical isolates

Several dimerics-triazine Schiff bases displayed more potent anti-bacterial activity compared with ampicillin trihydrate. They revealed significantly low MIC values towards the tested MDR strains and showed a high selectivity index towards antimicrobial activity againstK. pneumoniaeandMRSA1compared to mammalian cells.