Preparation of Tamsulosin Hydrochloride-Loaded Mucoadhesive In Situ Gelling Polymeric Formulation for Nasal Delivery in Geriatrics
This study aimed to prepare tamsulosin hydrochloride (HCl)-loaded in situ gelling formulation by using hydroxypropyl methylcellulose (HPMC), gellan gum, poloxamer 188, and benzalkonium chloride. Physicochemical evaluation of formulations included determination of pH, viscosity, gelation time, gel strength, drug content, and sterility. In silico study was performed to analyze interactions between polymers, drug, and mucin glycoprotein. In vitro degradation time, drug release, ex vivo mucoadhesion time, permeation, in vivo pharmacokinetics, and stability studies were performed to assess the formulation. Formulations were transparent and displayed acceptable physicochemical attributes. Tamsulosin HCl and polymers interacted via non-covalent interactions. HPMC formed hydrogen bonds, hydrophobic and van der Waals interactions with mucin protein while the drug formed hydrogen bonds only. Gel formulation degraded in simulated nasal fluid within 24 h. In situ gelling formulation showed 83.8 ± 1.7% drug release and remained adhered to the mucosa for 24.5 ± 1 h. A higher (~ 1.85 times) drug permeation was recorded through mucosa within 6 h by in situ gelling formulation when compared to control counterparts (aqueous solution of drug and in situ gelling formulation without poloxamer 188). Nasal administration of tamsulosin HCl by using in situ gelling formulation led to a ~ 3.3 and ~ 3.5 times, respectively, higher Cmax (maximum plasma concentration) and $ AUC_{total} $ (total area under the curve) than the orally administered aqueous solution. Relative bioavailability of drug delivered by nasal in situ gelling formulation was 3.5 times the oral counterpart. These results indicated that the prepared in situ gelling formulation can act as a promising candidate for systemic administration of tamsulosin HCl. Graphical Abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
AAPS PharmSciTech - 24(2023), 8 vom: 28. Nov. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rana, Sadia Jafar [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Benign prostate hyperplasia |
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| Anmerkungen: |
© The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1208/s12249-023-02700-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a This study aimed to prepare tamsulosin hydrochloride (HCl)-loaded in situ gelling formulation by using hydroxypropyl methylcellulose (HPMC), gellan gum, poloxamer 188, and benzalkonium chloride. Physicochemical evaluation of formulations included determination of pH, viscosity, gelation time, gel strength, drug content, and sterility. In silico study was performed to analyze interactions between polymers, drug, and mucin glycoprotein. In vitro degradation time, drug release, ex vivo mucoadhesion time, permeation, in vivo pharmacokinetics, and stability studies were performed to assess the formulation. Formulations were transparent and displayed acceptable physicochemical attributes. Tamsulosin HCl and polymers interacted via non-covalent interactions. HPMC formed hydrogen bonds, hydrophobic and van der Waals interactions with mucin protein while the drug formed hydrogen bonds only. Gel formulation degraded in simulated nasal fluid within 24 h. In situ gelling formulation showed 83.8 ± 1.7% drug release and remained adhered to the mucosa for 24.5 ± 1 h. A higher (~ 1.85 times) drug permeation was recorded through mucosa within 6 h by in situ gelling formulation when compared to control counterparts (aqueous solution of drug and in situ gelling formulation without poloxamer 188). Nasal administration of tamsulosin HCl by using in situ gelling formulation led to a ~ 3.3 and ~ 3.5 times, respectively, higher Cmax (maximum plasma concentration) and $ AUC_{total} $ (total area under the curve) than the orally administered aqueous solution. Relative bioavailability of drug delivered by nasal in situ gelling formulation was 3.5 times the oral counterpart. These results indicated that the prepared in situ gelling formulation can act as a promising candidate for systemic administration of tamsulosin HCl. Graphical Abstract | ||
| 650 | 4 | |a Benign prostate hyperplasia |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a gelling mucoadhesive formulation |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Nasal drug delivery |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Polymeric system |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Tamsulosin hydrochloride |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Zafar, Saman |4 aut | |
| 700 | 1 | |a Shahzad, Aqeel |4 aut | |
| 700 | 1 | |a Basit, Muhammad |4 aut | |
| 700 | 1 | |a Mudassir, Jahanzeb |4 aut | |
| 700 | 1 | |a Akhlaq, Muhammad |4 aut | |
| 700 | 1 | |a Chohan, Tahir Ali |4 aut | |
| 700 | 1 | |a Arshad, Muhammad Sohail |0 (orcid)0000-0001-9807-5841 |4 aut | |
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