A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling

Autor: Xuyu Chai, Jin Li, Li Yang, Chai Hongyu, Xiaoqiang Xiang, Tao Tao, Yan Zhao, Yunfan Zhao
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
Polymers
Physiology
Antibiotics
lcsh:Medicine
02 engineering and technology
Drug resistance
Pharmacology
030226 pharmacology & pharmacy
Delayed-Action Preparations
0302 clinical medicine
polycyclic compounds
Medicine and Health Sciences
lcsh:Science
Mammals
Multidisciplinary
Pulse (signal processing)
Pharmaceutics
Experimental Design
Hematology
021001 nanoscience & nanotechnology
Body Fluids
Chemistry
Blood
Macromolecules
Research Design
Anesthesia
Area Under Curve
Physical Sciences
Vertebrates
Engineering and Technology
Methacrylates
Anatomy
0210 nano-technology
medicine.drug
Research Article
Half-Life
Tablets
Drug Liberation
Drug Administration
medicine.drug_class
Materials by Structure
Drug Compounding
Materials Science
Research and Analysis Methods
Drug Absorption
Blood Plasma
03 medical and health sciences
Dogs
Pharmacokinetics
Drug Therapy
In vivo
Coatings
otorhinolaryngologic diseases
medicine
Animals
Humans
Materials by Attribute
business.industry
Surface Treatments
lcsh:R
Organisms
Biology and Life Sciences
Amoxicillin
Models
Theoretical
Polymer Chemistry
Manufacturing Processes
ROC Curve
Amniotes
Microscopy
Electron
Scanning
lcsh:Q
business
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 8, p e0160260 (2016)
ISSN: 1932-6203
Popis: Background Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients’ compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. Methods The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box–Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Results and Discussion Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box–Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog. Conclusions This study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box–Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms.
Databáze: OpenAIRE
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