Modulation of the Release of a Non-Interacting Low Solubility Drug from Chitosan Pellets Using Different Pellet Size, Composition and Numerical Optimization
Two size classes of piroxicam (PXC) pellets (mini (380–550 μm) and conventional (700–1200 μm)) were prepared using extrusion/spheronization and medium viscosity chitosan (CHS). Mixture experimental design and numerical optimization were applied to distinguish fo...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-04-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/11/4/175 |
| _version_ | 1828372513712766976 |
|---|---|
| author | Ioannis Partheniadis Paraskevi Gkogkou Nikolaos Kantiranis Ioannis Nikolakakis |
| author_facet | Ioannis Partheniadis Paraskevi Gkogkou Nikolaos Kantiranis Ioannis Nikolakakis |
| author_sort | Ioannis Partheniadis |
| collection | DOAJ |
| description | Two size classes of piroxicam (PXC) pellets (mini (380–550 μm) and conventional (700–1200 μm)) were prepared using extrusion/spheronization and medium viscosity chitosan (CHS). Mixture experimental design and numerical optimization were applied to distinguish formulations producing high sphericity pellets with fast or extended release. High CHS content required greater wetting liquid volume for pellet formation and the diameter decreased linearly with volume. Sphericity increased with CHS for low-to-medium drug content. Application of PXRD showed that the drug was a mixture of form II and I. Crystallinity decreased due to processing and was significant at 5% drug content. Raman spectroscopy showed no interactions. At pH 1.2, the dissolved CHS increased ‘apparent’ drug solubility up to 0.24 mg/mL while, at pH 5.6, the suspended CHS increased ‘apparent’ solubility to 0.16 mg/mL. Release at pH 1.2 was fast for formulations with intermediate CHS and drug levels. At pH 5.6, conventional pellets showed incomplete release while mini pellets with a CHS/drug ratio ≥2 and up to 21.25% drug, showed an extended release that was completed within 8 h. Numerical optimization provided optimal formulations for fast release at pH 1.2 with drug levels up to 40% as well as for extended release formulations with drug levels of 5% and 10%. The Weibull model described the release kinetics indicating complex or combined release (parameter ‘<i>b</i>’ > 0.75) for release at pH 1.2, and normal diffusion for the mini pellets at pH 5.6 (‘<i>b</i>’ from 0.63 to 0.73). The above results were attributed mainly to the different pellet sizes and the extensive dissolution/erosion of the gel matrix was observed at pH 1.2 but not at pH 5.6. |
| first_indexed | 2024-04-14T07:04:45Z |
| format | Article |
| id | doaj.art-6e826907045b40d5beca82f50e004d12 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-14T07:04:45Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6e826907045b40d5beca82f50e004d122022-12-22T02:06:35ZengMDPI AGPharmaceutics1999-49232019-04-0111417510.3390/pharmaceutics11040175pharmaceutics11040175Modulation of the Release of a Non-Interacting Low Solubility Drug from Chitosan Pellets Using Different Pellet Size, Composition and Numerical OptimizationIoannis Partheniadis0Paraskevi Gkogkou1Nikolaos Kantiranis2Ioannis Nikolakakis3Department of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Mineralogy-Petrology-Economic Geology, School of Geology, Faculty of Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceDepartment of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceTwo size classes of piroxicam (PXC) pellets (mini (380–550 μm) and conventional (700–1200 μm)) were prepared using extrusion/spheronization and medium viscosity chitosan (CHS). Mixture experimental design and numerical optimization were applied to distinguish formulations producing high sphericity pellets with fast or extended release. High CHS content required greater wetting liquid volume for pellet formation and the diameter decreased linearly with volume. Sphericity increased with CHS for low-to-medium drug content. Application of PXRD showed that the drug was a mixture of form II and I. Crystallinity decreased due to processing and was significant at 5% drug content. Raman spectroscopy showed no interactions. At pH 1.2, the dissolved CHS increased ‘apparent’ drug solubility up to 0.24 mg/mL while, at pH 5.6, the suspended CHS increased ‘apparent’ solubility to 0.16 mg/mL. Release at pH 1.2 was fast for formulations with intermediate CHS and drug levels. At pH 5.6, conventional pellets showed incomplete release while mini pellets with a CHS/drug ratio ≥2 and up to 21.25% drug, showed an extended release that was completed within 8 h. Numerical optimization provided optimal formulations for fast release at pH 1.2 with drug levels up to 40% as well as for extended release formulations with drug levels of 5% and 10%. The Weibull model described the release kinetics indicating complex or combined release (parameter ‘<i>b</i>’ > 0.75) for release at pH 1.2, and normal diffusion for the mini pellets at pH 5.6 (‘<i>b</i>’ from 0.63 to 0.73). The above results were attributed mainly to the different pellet sizes and the extensive dissolution/erosion of the gel matrix was observed at pH 1.2 but not at pH 5.6.https://www.mdpi.com/1999-4923/11/4/175pellets 1pellet diameter 2crystallinity 3sphericity 4fast release 5extended release 6 |
| spellingShingle | Ioannis Partheniadis Paraskevi Gkogkou Nikolaos Kantiranis Ioannis Nikolakakis Modulation of the Release of a Non-Interacting Low Solubility Drug from Chitosan Pellets Using Different Pellet Size, Composition and Numerical Optimization Pharmaceutics pellets 1 pellet diameter 2 crystallinity 3 sphericity 4 fast release 5 extended release 6 |
| title | Modulation of the Release of a Non-Interacting Low Solubility Drug from Chitosan Pellets Using Different Pellet Size, Composition and Numerical Optimization |
| title_full | Modulation of the Release of a Non-Interacting Low Solubility Drug from Chitosan Pellets Using Different Pellet Size, Composition and Numerical Optimization |
| title_fullStr | Modulation of the Release of a Non-Interacting Low Solubility Drug from Chitosan Pellets Using Different Pellet Size, Composition and Numerical Optimization |
| title_full_unstemmed | Modulation of the Release of a Non-Interacting Low Solubility Drug from Chitosan Pellets Using Different Pellet Size, Composition and Numerical Optimization |
| title_short | Modulation of the Release of a Non-Interacting Low Solubility Drug from Chitosan Pellets Using Different Pellet Size, Composition and Numerical Optimization |
| title_sort | modulation of the release of a non interacting low solubility drug from chitosan pellets using different pellet size composition and numerical optimization |
| topic | pellets 1 pellet diameter 2 crystallinity 3 sphericity 4 fast release 5 extended release 6 |
| url | https://www.mdpi.com/1999-4923/11/4/175 |
| work_keys_str_mv | AT ioannispartheniadis modulationofthereleaseofanoninteractinglowsolubilitydrugfromchitosanpelletsusingdifferentpelletsizecompositionandnumericaloptimization AT paraskevigkogkou modulationofthereleaseofanoninteractinglowsolubilitydrugfromchitosanpelletsusingdifferentpelletsizecompositionandnumericaloptimization AT nikolaoskantiranis modulationofthereleaseofanoninteractinglowsolubilitydrugfromchitosanpelletsusingdifferentpelletsizecompositionandnumericaloptimization AT ioannisnikolakakis modulationofthereleaseofanoninteractinglowsolubilitydrugfromchitosanpelletsusingdifferentpelletsizecompositionandnumericaloptimization |