Development and In Vitro Evaluation of Controlled Release Viagra<sup>®</sup> Containing Poloxamer-188 Using Gastroplus<sup>™</sup> PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments
Sildenafil is the active substance in Viagra<sup>®</sup> tablets, which is approved by the FDA to treat sexual dysfunction in men. Poor solubility and short half-life, however, can limit the span of its effectiveness. Therefore, this study focused on an oral controlled release matrix sys...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/14/5/479 |
| _version_ | 1797533607955267584 |
|---|---|
| author | Mosab Arafat Muhammad Sarfraz Salahdein AbuRuz |
| author_facet | Mosab Arafat Muhammad Sarfraz Salahdein AbuRuz |
| author_sort | Mosab Arafat |
| collection | DOAJ |
| description | Sildenafil is the active substance in Viagra<sup>®</sup> tablets, which is approved by the FDA to treat sexual dysfunction in men. Poor solubility and short half-life, however, can limit the span of its effectiveness. Therefore, this study focused on an oral controlled release matrix system with the aim to improve solubility, control the drug release, and sustain the duration of drug activity. The controlled release matrices were prepared with poloxamer-188, hydroxypropyl methylcellulose, and magnesium stearate. Various formulations of different ratios were developed, evaluated in vitro, and assessed in silico. Poloxamer-188 appeared to have a remarkable influence on the release profile of sildenafil citrate. In general, the rate of drug release decreased as the amount of polymer was gradually increased in the matrix system, achieving a maximum release period over 12 h. The in silico assessment by using the GastroPlus™ PBPK modeling software predicted a significant variation in C<sub>max,</sub> t<sub>max</sub>, t<sub>1/2</sub>, and AUC<sub>0-t</sub> among the formulations. In conclusion, the combination of polymers in matrix systems can have substantial impact on controlling and modifying the drug release pattern. |
| first_indexed | 2024-03-10T11:16:58Z |
| format | Article |
| id | doaj.art-4bd419ee2bb347b59c0142211ce6300e |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T11:16:58Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-4bd419ee2bb347b59c0142211ce6300e2023-11-21T20:18:36ZengMDPI AGPharmaceuticals1424-82472021-05-0114547910.3390/ph14050479Development and In Vitro Evaluation of Controlled Release Viagra<sup>®</sup> Containing Poloxamer-188 Using Gastroplus<sup>™</sup> PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic AssessmentsMosab Arafat0Muhammad Sarfraz1Salahdein AbuRuz2College of Pharmacy, Al Ain University, Al Ain P.O. Box 64141, United Arab EmiratesCollege of Pharmacy, Al Ain University, Al Ain P.O. Box 64141, United Arab EmiratesDepartment of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab EmiratesSildenafil is the active substance in Viagra<sup>®</sup> tablets, which is approved by the FDA to treat sexual dysfunction in men. Poor solubility and short half-life, however, can limit the span of its effectiveness. Therefore, this study focused on an oral controlled release matrix system with the aim to improve solubility, control the drug release, and sustain the duration of drug activity. The controlled release matrices were prepared with poloxamer-188, hydroxypropyl methylcellulose, and magnesium stearate. Various formulations of different ratios were developed, evaluated in vitro, and assessed in silico. Poloxamer-188 appeared to have a remarkable influence on the release profile of sildenafil citrate. In general, the rate of drug release decreased as the amount of polymer was gradually increased in the matrix system, achieving a maximum release period over 12 h. The in silico assessment by using the GastroPlus™ PBPK modeling software predicted a significant variation in C<sub>max,</sub> t<sub>max</sub>, t<sub>1/2</sub>, and AUC<sub>0-t</sub> among the formulations. In conclusion, the combination of polymers in matrix systems can have substantial impact on controlling and modifying the drug release pattern.https://www.mdpi.com/1424-8247/14/5/479sildenafil citratepoloxamer-188matrix systempolymercontrolled release |
| spellingShingle | Mosab Arafat Muhammad Sarfraz Salahdein AbuRuz Development and In Vitro Evaluation of Controlled Release Viagra<sup>®</sup> Containing Poloxamer-188 Using Gastroplus<sup>™</sup> PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments Pharmaceuticals sildenafil citrate poloxamer-188 matrix system polymer controlled release |
| title | Development and In Vitro Evaluation of Controlled Release Viagra<sup>®</sup> Containing Poloxamer-188 Using Gastroplus<sup>™</sup> PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments |
| title_full | Development and In Vitro Evaluation of Controlled Release Viagra<sup>®</sup> Containing Poloxamer-188 Using Gastroplus<sup>™</sup> PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments |
| title_fullStr | Development and In Vitro Evaluation of Controlled Release Viagra<sup>®</sup> Containing Poloxamer-188 Using Gastroplus<sup>™</sup> PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments |
| title_full_unstemmed | Development and In Vitro Evaluation of Controlled Release Viagra<sup>®</sup> Containing Poloxamer-188 Using Gastroplus<sup>™</sup> PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments |
| title_short | Development and In Vitro Evaluation of Controlled Release Viagra<sup>®</sup> Containing Poloxamer-188 Using Gastroplus<sup>™</sup> PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments |
| title_sort | development and in vitro evaluation of controlled release viagra sup r sup containing poloxamer 188 using gastroplus sup ™ sup pbpk modeling software for in vivo predictions and pharmacokinetic assessments |
| topic | sildenafil citrate poloxamer-188 matrix system polymer controlled release |
| url | https://www.mdpi.com/1424-8247/14/5/479 |
| work_keys_str_mv | AT mosabarafat developmentandinvitroevaluationofcontrolledreleaseviagrasupsupcontainingpoloxamer188usinggastroplussupsuppbpkmodelingsoftwareforinvivopredictionsandpharmacokineticassessments AT muhammadsarfraz developmentandinvitroevaluationofcontrolledreleaseviagrasupsupcontainingpoloxamer188usinggastroplussupsuppbpkmodelingsoftwareforinvivopredictionsandpharmacokineticassessments AT salahdeinaburuz developmentandinvitroevaluationofcontrolledreleaseviagrasupsupcontainingpoloxamer188usinggastroplussupsuppbpkmodelingsoftwareforinvivopredictionsandpharmacokineticassessments |