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Sains Malaysiana 53(11)(2024): 3747-3759 http://doi.org/10.17576/jsm-2024-5311-17
The Effects of
Different Solubilizing Agents on the Transport and Pharmacokinetic Profiles of
Indomethacin: in vitro and in vivo Approach
(Kesan Agen Pelarut Berbeza Terhadap Profil Pengangkutan dan Farmakokinetik Indometasin: Pendekatan in
vitro dan in vivo)
SITI
AISYAH ZAINUDDIN1,3, ABDUL LATIP AB HAMID1, AQILA IMAN
RAFANDI1, MASHANI MOHAMAD2,4, KHURIAH ABDUL HAMID1,4,* &
SYED HAROON KHALID1,4
1Department
of Pharmaceutical Technology, Faculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor, 42300 Puncak Alam,
Selangor, Malaysia
Diserahkan: 26 Julai 2024/Diterima: 27 September 2024
Abstract
The poor
water solubility of new chemical entities (NCEs) discovered in pharmaceutical
screening programs hampers their development and limits effective treatment
delivery. Solubilizing agents offer a direct approach to increase solubility
and oral bioavailability. This study employed indomethacin as a model drug from
Biopharmaceutical Classification System (BCS) class II. Solubilizing agents,
including propylene glycol, Transcutol P, Labrasol, PEG 400, and Tween 80, were separately added at
10% (v/v) to 1 mg/5 mL for in vitro diffusion chamber and 10 mg/kg body
weight for in vivo oral absorption studies of indomethacin. Drug
concentrations were analysed using reversed-phase high-performance liquid
chromatography (HPLC). In vitro, 10% (v/v) labrasol,
PEG 400, and Tween 80 significantly (p<0.01) increased indomethacin
permeability across the rat intestinal layer. However, Transcutol P and PG (propylene glycol 10%v/v) showed no discernible impact on in vitro permeability. In the in vivo oral absorption study, PG (propylene glycol
10%v/v) and Transcutol P significantly (p<0.05)
enhanced indomethacin absorption, while 10% (v/v) labrasol,
PEG 400, and Tween 80 did not show significant effects. No in vitro-in vivo correlation (IVIVC) was observed, likely due to the physicochemical properties
of indomethacin and the complex physiological environment in the
gastrointestinal (GI) tract. Further investigations are necessary to
comprehensively understand the factors affecting indomethacin solubility and
absorption, considering both the drug’s properties and the GI tract’s
physiological conditions.
Keywords: Drug
transport; indomethacin; pharmacokinetic profiles; solubility; solubilizing
agents
Abstrak
Keterlarutan air yang rendah bagi entiti kimia baharu (NCEs) yang ditemui dalam program penyaringan farmaseutikal menghalang perkembangan ubatan tersebut dan mengehadkan keberkesanan rawatan. Agen pelarut menawarkan pendekatan langsung untuk meningkatkan keterlarutan dan bioketersediaan oral. Kajian ini menggunakan indometasin sebagai model sebatian ubat berdasarkan Sistem Pengelasan Biofarmaseutikal (BCS) kelas II. Setiap agen pelarut, termasuk propilena glikol, Transcutol P, Labrasol, PEG 400 dan Tween 80 pada kepekatan 10% (v/v) ditambah kepada 1
mg/5 mL sebatian indometasin secara berasingan untuk kajian resapan in vitro dan sebanyak 10 mg/kg berat badan diberikan kepada tikus untuk kajian penyerapan sebatian indometasin secara oral. Sebatian indometasin dianalisis menggunakan kaedah kromatografi cecair berprestasi tinggi – fasa terbalik (KCPT-Fasa Terbalik). Dalam kajian in vitro, sebanyak 10% (v/v) labrasol, PEG
400 dan Tween 80 telah meningkatkan kebolehtelapan indometasin merentasi lapisan usus tikus dengan signifikan (p<0.01). Walau bagaimanapun, 10% (v/v) propilena glikol dan Transcutol P tidak menunjukkan kesan yang signifikan terhadap kebolehtelapan melalui kajian in vitro. Dalam kajian penyerapan oral secara in vivo, 10% (v/v) propilena glikol dan Transcutol P meningkatkan penyerapan sebatian indometasin secara signifikan (p<0.05), manakala 10% (v/v) labrasol, PEG 400 dan Tween 80 tidak menunjukkan kesan yang signifikan. Keputusan kajian menunjukkan tiada korelasi in vitro-in
vivo (IVIVC), berkemungkinan disebabkan oleh sifat fizikokimia indometasin dan persekitaran fisiologi yang kompleks dalam saluran gastrointestinal
(GI). Kajian lanjut diperlukan untuk memahami secara menyeluruh faktor yang mempengaruhi keterlarutan dan penyerapan indometasin dengan mempertimbangkan kedua-dua sifat sebatian dan keadaan fisiologi saluran GI.
Kata kunci: Pengangkutan ubat; indometasin; profil farmakokinetik; keterlarutan; agen pelarut
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