Formulation and Bioequivalence Testing of Fixed-Dose Combination Orally Disintegrating Tablets for the Treatment of Tuberculosis in the Paediatric Population

Dennison, Thomas J.; Smith, Julian C.; Badhan, Raj; Mohammed, Afzal-Ur-Rahman

doi:10.1016/j.xphs.2020.07.016

Cited by 12 publications

(10 citation statements)

References 39 publications

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“…Its ability to inhibit RNA polymerase was through interaction with the switch region of RNA polymerase; while Rifampicin inhibited the same enzyme through different region. [52] Myxopyronin showed no phototoxicity and mutagenicity in rabbit animal models during the preclinical trials stage, in the present study. Rare adverse effects including mild diarrhea and cholestatic jaundice were reported in less than 5 % of the experimental subjects received the test antibiotics during randomized human clinical trials phases 1/2.…”

Section: Discusssupporting

confidence: 50%

Screening and the Industry of Myxopyronin B Antibiotic from Different Soil Environments in Egypt

Kassab

2024

Preprint

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Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

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Section: Discusssupporting

confidence: 50%

Screening and the Industry of Myxopyronin B Antibiotic from Different Soil Environments in Egypt

Kassab

2024

Preprint

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“…Its ability to inhibit RNA polymerase was through interaction with the switch region of RNA polymerase; while Rifampicin inhibited the same enzyme through different region. [52] Corallopyronin A showed no phototoxicity and mutagenicity in rabbit animal models during the preclinical trials stage, in the present study. Rare adverse effects including cholestatic jaundice were reported in less than 5 % of the experimental subjects received the test antibiotics during randomized human clinical trials phases 1/2.…”

Section: Discusssupporting

confidence: 47%

Exhibition of Corallopyronin A an Antibiotic from Different Soil Environments in Egypt

Kassab

2024

Preprint

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Background: Across the world, antibiotic resistance is a critical challenge. To address such a problem, it has to be done to investigate new antibiotic sources. Aim of the study: Study of the antibacterial activity of Corallopyronin A in preclinical animal testing and randomized human clinical trials stages 1/2, as well as investigating the purification of Corallopyronin A from different soil conditions in Egypt. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were tested to develop bacterial isolates that produced the antibiotic compound Corallopyronin A. Reversed phase HPLC was used to purify Myxopyronin A. The broth microdilution method and the paper disc diffusion assay determined the test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in phases 1/2 of randomized clinical studies involving humans and animal models. Results: Corallopyronin A was generated from the culture supernatant of the soil bacterial isolate Corallococcus coralloides M2, cultivated on a Casein yeast peptone( CYP) plate. The test antibiotic prevented the growth of several Gram-ve bacteria, including Escherichia coli, at MICs higher than 100 mcg/ ml; while blocking the development of many Gram +ve bacteria, with MICs ranging from 3 to 15 mcg/ ml. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. A bactericidal consequence of the test antibiotic was detected in the inhibition of prokaryotic DNA-dependent RNA polymerase( RNLP). Conclusion: The synthesis of the bactericidal antibiotic Corallopyronin A from Corallococcus coralloides M2 isolated from different soil settings in Egypt intrigued the current investigation.

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“…Although the gastric emptying characteristics of pellets in ODTs have been reported, , the information appears insufficient for precise prediction of drug absorption from ODTs in humans without coadministration of water. Other studies , predicted the in vivo performance of fixed dose combination ODTs, in which a commercial in silico model (Simcyp) and in vitro biorelevant dissolution testing using a USP Apparatus II with 50 rpm were coupled.…”

Section: Orally Administered Dds Formulationsmentioning

confidence: 99%

In Silico Modeling Approaches Coupled with In Vitro Characterization in Predicting In Vivo Performance of Drug Delivery System Formulations

Kambayashi

2023

Mol. Pharmaceutics

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Optimization of the in vivo performance of dosage forms in humans is essential in developing not only conventional formulations but also drug delivery system (DDS) formulations. Although animal experiments are still useful for these formulations, in silico approaches have become increasingly important for DDS formulations with regard to species-specific differences in physiology that can affect the in vivo performance of dosage forms between animals and humans. Furthermore, it is also important to couple in vitro characterizations with in silico models to predict in vivo performance in humans precisely. In this review article, I summarized in vitro−in silico approaches to predicting the in vivo performance of oral DDS formulations (amorphous solid dispersions, lipid-based formulations, nanosized formulations, cyclodextrins-based formulations, sustained release products, enteric coat products, and orally disintegrating tablets) and parenteral DDS formulations (cyclodextrins-based formulations, liposomes, and inhaled formulations).

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Formulation and Bioequivalence Testing of Fixed-Dose Combination Orally Disintegrating Tablets for the Treatment of Tuberculosis in the Paediatric Population

Cited by 12 publications

References 39 publications

Screening and the Industry of <em>Myxopyronin B</em> Antibiotic from Different Soil Environments in Egypt

Screening and the Industry of <em>Myxopyronin B</em> Antibiotic from Different Soil Environments in Egypt

Exhibition of <em>Corallopyronin A </em>an Antibiotic from Different Soil Environments in Egypt

In Silico Modeling Approaches Coupled with In Vitro Characterization in Predicting In Vivo Performance of Drug Delivery System Formulations

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