Modelling and Simulation of the Drug Release from a Solid Dosage Form in the Human Ascending Colon: The Influence of Different Motility Patterns and Fluid Viscosities

For colonic drug delivery, the ascending part of the colon is the most favourable site as it offers the most suitable environmental conditions for drug dissolution. Commonly, the performance of a drug formulation is assessed using standardised dissolution apparatus, which does not replicate the hydrodynamics and shear stress evoked by wall motion in the colon. In this work, computer simulations are used to analyse and understand the influence of different biorelevant motility patterns on the disintegration/drug release of a solid dosage form (tablet) under different fluid conditions (viscosities) to mimic the ascending colonic environment. Furthermore, the ability of the motility pattern to distribute the drug in the ascending colon luminal environment is analysed to provide data for a spatiotemporal concentration profile. The motility patterns used are derived from in vivo data representing different motility patterns in the human ascending colon. The applied motility patterns show considerable differences in the drug release rate from the tablet, as well as in the ability to distribute the drug along the colon. The drug dissolution/disintegration process from a solid dosage form is primarily influenced by the hydrodynamic and shear stress it experiences, i.e., a combination of motility pattern and fluid viscosity. Reduced fluid motion leads to a more pronounced influence of diffusion in the tablet dissolution process. The motility pattern that provoked frequent single shear stress peaks seemed to be more effective in achieving a higher drug release rate. The ability to simulate drug release profiles under biorelevant colonic environmental conditions provides valuable feedback to better understand the drug formulation and how this can be optimised to ensure that the drug is present in the desired concentration within the ascending colon.

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In-Vitro Functionality of Clozapine Biphasic Release Minitablet Using Advanced Statistical Tools

Drug Delivery Letters ◽

10.2174/2210303111666210412163605 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hardik Rana ◽

Rushikesh Chaudhari ◽

Vaishali Thakkar ◽

Tejal Gandhi

Keyword(s):

Drug Release ◽

Sustained Release ◽

Ethyl Cellulose ◽

Dosage Form ◽

Immediate Release ◽

Solid Dosage Form ◽

Solid Dosage ◽

Precipitation Inhibitor

Background: The better control of the drug release with immediate effect is the major concern to achieve better therapeutic action and patient compliance. The failure of the solid dispersion complex during storage as well as in-vivo is another concern for the oral solid dosage form. Objective: The prime objective of the present study was to optimize the biphasic minitablet incorporating quality by design approach using the combination of waxy erodible and water-impermeable excipients. Exploration of Soluplus as a precipitation inhibitor and Dexolve as a solubility enhancer in oral solid dosage form was the secondary objective. Methods: The drug-Excipient compatibility study was assessed by FTIR. Clozapine was chosen as a model drug that has poor aqueous solubility. The complex was formulated using B-cyclodextrin or HP B-CD or Dexolve by kneading method. The screening of solubility enhancers and their amount were performed based on phase solubility study. The precipitation inhibitor was screened as per the parachute effect study. Immediate release minitablets were formulated using a direct compression method using different disintegrating agents. The IR minitablets were evaluated for different evaluation parameters. The sustained release minitablets was formulated by hot-melt granulation technique incorporating the Precirol ATO 5 as a waxy excipient and ethyl cellulose as water impermeable excipient. The SR minitablet was optimized using a central composite design. The amount of Precirol ATO 5 and ethyl cellulose were chosen as independent variables and % drug release at 1, 6, and 10 h was selected as responses. The designed batches were evaluated for different pre and post compressional parameters. The IR and SR minitablets were filled in a capsule as per dose requirement and evaluated for in-vitro drug release. The in-vivo plasma concentration was predicted using the Back calculation of the Wagner – Nelson approach. Results: Drug – Excipient study revealed that no significant interaction was observed. Dexolve was screened as a solubility enhancer for the improvement of the solubility of clozapine. The Soluplus was chosen as a precipitation inhibitor from the parachute effect study. The immediate-release tablet was formulated using Prosolv EASYtab SP yield less disintegration time with better flowability. The sustained release mini-tablet was formulated using Precirol ATO 5 and ethyl cellulose. Two-dimensional and three-dimensional plots were revealed the significant effect of the amount of Precirol ATO 5 and ethyl cellulose. The overlay plot locates the optimized region. The in-vitro drug release study revealed the desired drug release of the final combined formulation. The in-vivo plasma concentration-time confirms the drug release up to 12h. Conclusion: The biphasic mini-tablets were formulated successfully for better control of drug release leads to high patient compliance. The use of soluplus as a precipitation inhibitor is explored in the oral solid dosage form for a poorly aqueous drug. Prosolv EASYtab SP was incorporated in the formulation as super disintegrant. The amount of Precirol ATO 5 and ethyl cellulose had a significant effect on drug release in sustained-release minitablet. The approach can be useful in the industry.

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Carbopol 71G-NF polymer –The next pillar of oral solid dosage form

10.30574/msarr.2020.1.1.0018 ◽

2020 ◽

Vol 1 (1) ◽

pp. 010-017

Author(s):

R. Priyanka ◽

R. Senthil Prabhu

Keyword(s):

Molecular Weight ◽

Drug Release ◽

Acrylic Acid ◽

High Molecular Weight ◽

Dosage Form ◽

Carboxyl Groups ◽

Dry Powders ◽

Solid Dosage Form ◽

Solid Dosage ◽

Pharmaceutical Application

For pharmaceutical Oral Solid Dosage Form (OSDF) there are lots of excipients used and these excipients influence the drug release. In the recent decades there has been considerable interest in using carbopol polymers as excipients in a distinctive range of pharmaceutical application. Carbopol polymers are high molecular weight, cross linked, acrylic, acid-based polymers. Carbopol homopolymers are polymers of acrylic acid cross linked with ally sucrose or allylPentaerythritol. These polymers are offered as fluffy, white, dry powders. The carboxyl groups provided by the acrylic acid backbone of the polymer are responsible for many of the product benefits. This review work aims at guesstimate the characteristic of Carbopol 71G-NF polymer to be used as excipients in oral solid dosage form (OSDF).

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Solid dosage form preparations from oily medicines and their drug release. Effect of degree of surface-modification of silica gel on the drug release from phytonadione-loaded silica gels

Journal of Controlled Release ◽

10.1016/s0168-3659(00)00229-7 ◽

2000 ◽

Vol 67 (2-3) ◽

pp. 369-384 ◽

Cited By ~ 30

Author(s):

Makoto Otsuka ◽

Kana Tokumitsu ◽

Yoshihisa Matsuda

Keyword(s):

Surface Modification ◽

Drug Release ◽

Silica Gel ◽

Dosage Form ◽

Silica Gels ◽

Solid Dosage Form ◽

Solid Dosage

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Liquisolid Systems: A Review

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2010.3.1.1 ◽

2010 ◽

Vol 3 (1) ◽

pp. 795-802 ◽

Cited By ~ 1

Author(s):

Ajit S Kulkarni ◽

Nagesh H Aloorkar ◽

Madhav S. Mane ◽

Jayashree B. Gaja

Keyword(s):

Dissolution Rate ◽

Dosage Form ◽

Drug Dissolution ◽

Solid Dosage Form ◽

Solid Dosage ◽

Dissolution Properties ◽

Volatile Liquid ◽

Insoluble Drugs ◽

New Formulation ◽

Liquisolid Compacts

Liquisolid technique is a new and promising method that can change the dissolution rate of water insoluble drugs. According to the new formulation method of liquisolid compacts, liquid medications such as solutions or suspensions of water insoluble drugs in suitable non-volatile liquid vehicles can be converted into acceptably flowing and compressible powders by blending with selected powder excipients. It has been speculated that such systems exhibit enhanced release profiles. In this case, even though the drug is in a solid dosage form, it is held within the powder substrate in solution or, in a solubilized, almost molecularly dispersed state, which contributes to the enhanced drug dissolution properties.

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