Investigation of Solid Dosage Form Components Interaction Using Orthogonal Techniques- Discovery of New Forms of Sodium Stearyl Fumarate

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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A 3D printed bilayer oral solid dosage form combining metformin for prolonged and glimepiride for immediate drug delivery

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2018.04.020 ◽

2018 ◽

Vol 120 ◽

pp. 40-52 ◽

Cited By ~ 47

Author(s):

Christos I. Gioumouxouzis ◽

Apostolos Baklavaridis ◽

Orestis L. Katsamenis ◽

Catherine K. Markopoulou ◽

Nikolaos Bouropoulos ◽

...

Keyword(s):

Drug Delivery ◽

Dosage Form ◽

Solid Dosage Form ◽

Solid Dosage ◽

3D Printed

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Hot-Melt 3D Extrusion for the Fabrication of Customizable Modified-Release Solid Dosage Forms

Pharmaceutics ◽

10.3390/pharmaceutics12080738 ◽

2020 ◽

Vol 12 (8) ◽

pp. 738 ◽

Cited By ~ 1

Author(s):

Jaemin Lee ◽

Chanwoo Song ◽

Inhwan Noh ◽

Sangbyeong Song ◽

Yun-Seok Rhee

Keyword(s):

Dissolution Rate ◽

Dosage Form ◽

Amorphous State ◽

Dosage Forms ◽

Modified Release ◽

Solid Dosage Forms ◽

Solid Dosage Form ◽

Solid Dosage ◽

Enhanced Solubility ◽

Hot Melt

In this work, modified-release solid dosage forms were fabricated by adjusting geometrical properties of solid dosage forms through hot-melt 3D extrusion (3D HME). Using a 3D printer with air pressure driving HME system, solid dosage forms containing ibuprofen (IBF), polyvinyl pyrrolidone (PVP), and polyethylene glycol (PEG) were printed by simultaneous HME and 3D deposition. Printed solid dosage forms were evaluated for their physicochemical properties, dissolution rates, and floatable behavior. Results revealed that IBF content in the solid dosage form could be individualized by adjusting the volume of solid dosage form. IBF was dispersed as amorphous state with enhanced solubility and dissolution rate in a polymer solid dosage form matrix. Due to absence of a disintegrant, sustained release of IBF from printed solid dosage forms was observed in phosphate buffer at pH 6.8. The dissolution rate of IBF was dependent on geometric properties of the solid dosage form. The dissolution rate of IBF could be modified by merging two different geometries into one solid dosage form. In this study, the 3D HME process showed high reproducibility and accuracy for preparing dosage forms. API dosage and release profile were found to be customizable by modifying or combining 3D modeling.

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