Sains Malaysiana 51(10)(2022): 3271-3284

http://doi.org/10.17576/jsm-2022-5110-13

Physicochemical and Pharmacokinetic Evaluation of Praziquantel Co-Crystals by Varying the Spacer Group of Co-Crystal Formers

(Penilaian Fizikokimia dan Farmakokinetik Gabungan Hablur Praziquantel dengan Mempelbagaikan Kumpulan Penjarak Pembentuk Gabungan Hablur)

MUHAMMAD WASIM^1,*, ABDUL MANNAN¹, TABINDA AZIM², RASHID ALI KHAN³, GHALLAB ALOTAIBI⁴, MUHAMMAD AMER⁵, MUHAMMAD SHAFIQUE⁴, MUHAMMAD ASGHAR KHAN⁶, SUMAIRA GUL⁷ & IZHAR HUSSAIN¹

¹Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 45550, Pakistan

²Department of Pharmacy, Iqra University Islamabad Campus, Islamabad, Pakistan

³Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan

⁴Department of Pharmaceutical Sciences, College of Pharmacy, Al-Dawadmi Campus, Shaqra University, Shaqra, KSA

⁵Department of Pharmacy, Abasyn University Islamabad Campus, Islamabad, Pakistan

⁶Department of Pharmacy, University of Malakand, Chakdara 18800, Pakistan

⁷Department of Pharmacy, Abdul Wali Khan University Mardan, 23200, Pakistan

Received: 18 Jan 2022/Accepted: 23 May 2022

Abstract

The research work focuses on investigating the effects of spacer group (varying aliphatic chain length=n) of co-crystal formers (oxalic acid (OA, n=0), (malonic acid (MA, n=1), (succinic acid (SA, n=2), (glutaric acid (GA, n=3), and (adipic acid (AA, n=4) on the physicochemical properties and oral bioavailability of praziquantel (PZQ) co-crystals. For this purpose, different co-crystals of PZQ with dicarboxylic acid co-crystal formers (OA, MA, SA, GA, and AA) were synthesized. These co-crystals were characterized by powder X-ray diffractometry (XRPD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and thermogravimetry (TG) techniques. The in-vitro (solubility and dissolution) and in-vivo pharmacokinetic (P.K) studies were performed for PZQ co-crystals. Additionally, the effect of polymer hydroxypropyl cellulose (HPC) on the formation of PZQ co-crystals was also investigated. According to the study results, PZQ-SA co-crystal showed improved solubility, dissolution, and oral bioavailability. Overall, the solubility, dissolution, and oral bioavailability are consistent with each other. The order of improved solubility, dissolution, and oral bioavailability is observed as consistent like PZQ-SA > PZQ-AA > PZQ-GA > PZQ-OA > PZQ-MA > pure PZQ. Concerning HPC polymer effects, PZQ-OA, PZQ-MA, PZQ-GA, and PZQ-AA co-crystals were formed successfully in the presence of HPC polymer but the PZQ-SA co-crystal was inhibited.

Keywords: Co-crystal; pharmacokinetic parameters; physicochemical properties; spacer group

Abstrak

Penyelidikan ini memberi tumpuan kepada kajian kesan kumpulan penjarak (pelbagai panjang rantai alifatik=n) pembentuk gabungan hablur (asid oksalik (OA, n=0), (asid malonik (MA, n=1), (asid suksinik (SA, n=2), (asid glutarik (GA, n=3) dan (asid adipik (AA, n=4) pada sifat fizikokimia dan bioketersediaan oral bersama gabungan hablur praziquantel (PZQ). Untuk tujuan ini, gabungan hablur berbeza PZQ dengan pembentuk gabungan hablur asid dikarboksilik (OA, MA, SA, GA dan AA) telah disintesis. Gabungan hablur ini dicirikan oleh difraktometri sinar-X serbuk (XRPD), kalorimetri pengimbasan pembezaan (DSC), teknik spektroskopi inframerah transformasi Fourier (FT-IR) dan termogravimetri (TG). Kajian in-vitro (keterlarutan dan pelarutan) dan farmakokinetik in-vivo (P.K) telah dilakukan untuk gabungan hablur PZQ. Selain itu, kesan polimer hidroksipropil selulosa (HPC) pada pembentukan gabungan hablur PZQ turut dikaji. Menurut hasil kajian, gabungan hablur PZQ-SA menunjukkan kebolehgunaan sol yang lebih baik, pembubaran dan bioketersediaan oral. Secara keseluruhan, keterlarutan, pembubaran dan bioketersediaan oral adalah konsisten antara satu sama lain. Urutan keterlarutan, pelarutan dan bioketersediaan oral yang lebih baik diperhatikan sebagai konsisten seperti PZQ-SA > PZQ-AA > PZQ-GA > PZQ-OA > PZQ-MA > PZQ tulen. Mengenai kesan polimer HPC, gabungan hablur PZQ-OA, PZQ-MA, PZQ-GA dan PZQ-AA telah terbentuk dengan jayanya dengan kehadiran polimer HPC tetapi gabungan hablur PZQ-SA telah dihalang.

Kata kunci: Gabungan hablur; kumpulan penjarak; parameter farmakokinetik; sifat fizikokimia

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^*Corresponding author; email: wassypharmacist@gmail.com