SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™
The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full facto...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.974715/full |
| _version_ | 1811195701552480256 |
|---|---|
| author | Muhammad Talha Saleem Muhammad Harris Shoaib Rabia Ismail Yousuf Farrukh Rafiq Ahmed Kamran Ahmed Fahad Siddiqui Zafar Alam Mahmood Muhammad Sikandar Muhammad Suleman Imtiaz |
| author_facet | Muhammad Talha Saleem Muhammad Harris Shoaib Rabia Ismail Yousuf Farrukh Rafiq Ahmed Kamran Ahmed Fahad Siddiqui Zafar Alam Mahmood Muhammad Sikandar Muhammad Suleman Imtiaz |
| author_sort | Muhammad Talha Saleem |
| collection | DOAJ |
| description | The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK “ACAT” model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies. |
| first_indexed | 2024-04-12T00:47:25Z |
| format | Article |
| id | doaj.art-b1039c5735424c36a3ed0e70d856e84b |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T00:47:25Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b1039c5735424c36a3ed0e70d856e84b2022-12-22T03:54:50ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.974715974715SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™Muhammad Talha SaleemMuhammad Harris ShoaibRabia Ismail YousufFarrukh Rafiq AhmedKamran AhmedFahad SiddiquiZafar Alam MahmoodMuhammad SikandarMuhammad Suleman ImtiazThe study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK “ACAT” model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies.https://www.frontiersin.org/articles/10.3389/fphar.2022.974715/fulltramadolSeDeM diagram expert systemPBPKosmotic tabletcontrolled releasegastroplus |
| spellingShingle | Muhammad Talha Saleem Muhammad Harris Shoaib Rabia Ismail Yousuf Farrukh Rafiq Ahmed Kamran Ahmed Fahad Siddiqui Zafar Alam Mahmood Muhammad Sikandar Muhammad Suleman Imtiaz SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™ Frontiers in Pharmacology tramadol SeDeM diagram expert system PBPK osmotic tablet controlled release gastroplus |
| title | SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™ |
| title_full | SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™ |
| title_fullStr | SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™ |
| title_full_unstemmed | SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™ |
| title_short | SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™ |
| title_sort | sedem tool driven full factorial design for osmotic drug delivery of tramadol hcl formulation development physicochemical evaluation and in silico pbpk modeling for predictive pharmacokinetic evaluation using gastroplus™ |
| topic | tramadol SeDeM diagram expert system PBPK osmotic tablet controlled release gastroplus |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.974715/full |
| work_keys_str_mv | AT muhammadtalhasaleem sedemtooldrivenfullfactorialdesignforosmoticdrugdeliveryoftramadolhclformulationdevelopmentphysicochemicalevaluationandinsilicopbpkmodelingforpredictivepharmacokineticevaluationusinggastroplus AT muhammadharrisshoaib sedemtooldrivenfullfactorialdesignforosmoticdrugdeliveryoftramadolhclformulationdevelopmentphysicochemicalevaluationandinsilicopbpkmodelingforpredictivepharmacokineticevaluationusinggastroplus AT rabiaismailyousuf sedemtooldrivenfullfactorialdesignforosmoticdrugdeliveryoftramadolhclformulationdevelopmentphysicochemicalevaluationandinsilicopbpkmodelingforpredictivepharmacokineticevaluationusinggastroplus AT farrukhrafiqahmed sedemtooldrivenfullfactorialdesignforosmoticdrugdeliveryoftramadolhclformulationdevelopmentphysicochemicalevaluationandinsilicopbpkmodelingforpredictivepharmacokineticevaluationusinggastroplus AT kamranahmed sedemtooldrivenfullfactorialdesignforosmoticdrugdeliveryoftramadolhclformulationdevelopmentphysicochemicalevaluationandinsilicopbpkmodelingforpredictivepharmacokineticevaluationusinggastroplus AT fahadsiddiqui sedemtooldrivenfullfactorialdesignforosmoticdrugdeliveryoftramadolhclformulationdevelopmentphysicochemicalevaluationandinsilicopbpkmodelingforpredictivepharmacokineticevaluationusinggastroplus AT zafaralammahmood sedemtooldrivenfullfactorialdesignforosmoticdrugdeliveryoftramadolhclformulationdevelopmentphysicochemicalevaluationandinsilicopbpkmodelingforpredictivepharmacokineticevaluationusinggastroplus AT muhammadsikandar sedemtooldrivenfullfactorialdesignforosmoticdrugdeliveryoftramadolhclformulationdevelopmentphysicochemicalevaluationandinsilicopbpkmodelingforpredictivepharmacokineticevaluationusinggastroplus AT muhammadsulemanimtiaz sedemtooldrivenfullfactorialdesignforosmoticdrugdeliveryoftramadolhclformulationdevelopmentphysicochemicalevaluationandinsilicopbpkmodelingforpredictivepharmacokineticevaluationusinggastroplus |