Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Enhancement of the Solubility of Asenapine Maleate Through the Preparation of Co-Crystals

Author(s): Suhair S. Al-Nimry* and Mai S. Khanfar

Volume 19, Issue 7, 2022

Published on: 11 January, 2022

Page: [788 - 800] Pages: 13

DOI: 10.2174/1567201818666210805154345

Price: $65

Abstract

Background: Asenapine maleate, an anti-schizophrenic drug, is a class II drug with low solubility and high permeability. This exerts a rate-limiting effect on drug bioavailability.

Objective: To improve the solubility/dissolution rate of asenapine maleate and hence the bioavailability using the co-crystal approach.

Methods: Co-crystals were prepared using the solvent evaporation method. Since the drug has Hbond acceptor count of 6, and H-bond donor count of 2, several co-formers (nicotinamide, urea, succinic, benzoic, and citric acid) were investigated in different ratios. The optimized co-crystals (drug-nicotinamide in a ratio of 1:3) were evaluated using PXRD, DSC, FTIR spectroscopy, and SEM. Additionally, in vitro dissolution and stability studies were conducted.

Results: Preparation of the co-crystals was successful except when citric and benzoic acids were used. PXRD patterns showed that the co-crystals were crystalline. FTIR spectroscopy confirmed the formation of H-bond between the drug and the co-former. DSC indicated a lower melting point than that of the components followed immediately by an exothermic peak, which confirmed the formation of co-crystals. SEM showed the formation of crystals with different size and habit. The dissolution of the drug from all the prepared co-crystals was almost similar and much enhanced compared to that of the unprocessed drug. The initial dissolution of the drug from the optimized batch was much faster than that from the other co-crystals and the physical mixture with the same ratio. The optimized batch exhibited long term stability.

Conclusion: Co-crystals with improved solubility/dissolution rate of asenapine maleate were prepared successfully and were expected to enhance the bioavailability of the drug.

Keywords: Asenapine maleate, enhancement of the solubility, co-formers, co-crystals, schizophrenia, bipolar disorders.

« Previous Next »
Graphical Abstract

[1]
Avachat, A.M.; Kapure, S.S. Asenapine maleate in situ forming biodegradable implant: An approach to enhance bioavailability. Int. J. Pharm., 2014, 477(1-2), 64-72.
[2]
Kulkarni, J.A.; Avachat, A.M.; Avachat, C.M. Preferential formulation of second generation antipsychotic asenapine as inclusion complex with sulphobutylether-βCD (captisol): in vitro and in vivo evaluation. Curr. Drug Deliv., 2018, 15(4), 520-531.
[3]
Gambhire, V.M.; Ranpise, N.S. Enhanced oral delivery of asenapine maleate from solid lipid nanoparticles: pharmacokinetic and brain distribution evaluations. Asian J. Pharm. Sci., 2018, 12(3), 152-161.
[4]
Managuli, R.S.; Gourishetti, K.; Shenoy, R.R.; Koteshwara, K.B.; Reddy, M.S.; Mutalik, S. Preclinical pharmacokinetics and biodistribution studies of asenapine maleate using novel and sensitive RP–HPLC method. Bioanalysis, 2017, 9(14), 1037-1047.
[5]
Shreya, A.B.; Managuli, R.S.; Menon, J.; Kondapalli, L.; Hegde, A.R.; Avadhani, K. Nano-transfersomal formulations for transdermal delivery of asenapine maleate: in vitro and in vivo performance evaluations. J. Liposome Res., 2016, 26(3), 221-232.
[6]
Singh, S.K.; Dadhania, P.; Vuddanda, P.R.; Jain, A.; Velagac, S.; Singh, S. Intranasal delivery of asenapine loaded nanostructured lipid carriers: formulation, characterization, pharmacokinetic and behavioural assessment. RSC Adv., 2016, 6, 2032-2045.
[7]
Kulkarni, J.A.; Avachat, A.M. Pharmacodynamic and pharmacokinetic investigation of cyclodextrin mediated asenapine maleate in situ nasal gel for improved bioavailability. Drug Dev. Ind. Pharm., 2017, 43(2), 234-245.
[8]
SAPHRIS® Product Information. Merck Sharp & Dohme (Australia) Pty Limited. (Accessed 21 April 2019).
[9]
Managuli, R.S.; Wang, J.T.; Faruqu, F.N.; Kushwah, V.; Raut, S.Y.; Shreya, A.B. Asenapine maleate-loaded nanostructured lipid carriers: optimization and in vitro, ex vivo and in vivo evaluations. Nanomedicine (Lond.), 2018, 14(7), 889-910.
[10]
Singh, S.K.; Kosuru, R.; Dewangan, H.K.; Singh, S. An overview on asenapine maleate: Pk-Pd, preclinical and clinical update. Pharmasociety, 2015, 11, 110-115.
[11]
Patel, P.; Makwana, S.; Jobanputra, U.; Ravat, M.; Ajmera, A.; Patel, M. Sublingual route for the systemic delivery of Ondansetron. Int. J. Drug Dev. Res., 2011, 3(4), 36-44.
[12]
Singh, S.K.; Vijayakumar, M.R.; Singh, S. Intranasal delivery of asenapine loaded nanostructured lipid carriers for treatment of schizophrenia. J. Nanomed. Nanotechnol., 2014, 5(5), 256.
[13]
Naik, B.; Gandhi, J.; Shah, P.; Naik, H.; Sarolia, J. Asenapine maleate loaded solid lipid nanoparticles for oral delivery. Int. Res. J. Pharm., 2017, 8(11), 45-53.
[14]
Singh, R.P.; Narke, R.M.; Jadhav, P.V. Formulation and evaluation of asenapine maleate loaded niosomes for the treatment of schizophrenia. Indian J. Pharm. Educ., 2020, 54(2), S128-S139.
[15]
Patel, M.H.; Mundada, V.P.; Sawant, K.K. Novel drug delivery approach via self-microemulsifying drug delivery system for enhancing oral bioavailability of asenapine maleate: optimization, characterization, cell uptake, and in vivo pharmacokinetic studies. AAPS PharmSciTech., 2019, 20(2), 44.
[16]
Avasarala, H.; Dinakaran, S.K.; Kakaraparthy, R.; Jayanti, V.R. Self emulsifying drug delivery system for enhanced solubility of asenapine maleate: design, characterization, in vitro, ex vivo and in vivo appraisal. Drug Dev. Ind. Pharm., 2019, 45(4), 548-559.
[17]
Managuli, R.S.; Wang, J.T-Z.; Faruqu, F.M.; Pandey, A.; Jain, S.; Al-Jamal, K.T. Surface engineered nanoliposomal platform for selective lymphatic uptake of asenapine maleate: In vitro and in vivo studies. Mater. Sci. Eng. C, 2018, 109, 110620.
[18]
Supriya, A.; Sundaraseelan, J.; Murthy, B.R.S.; Priya, M.B. Formulation and evaluation of capsules of asenapine maleate loaded chitosan nanoparticles. Acta Sci. Pharm. Sci., 2018, 2(3), 29-37.
[19]
Chowdary, A.K.; Suravarapu, N.L.R.; Meddala, S. Formulation and characterization of asenapine maleate nanoparticles. Int. J. Pharm. Sci. Rev. Res., 2016, 40(1), 1-5.
[20]
Karagianni, A.; Malamatari, M.; Kachrimanis, K. Pharmaceutical cocrystals: new solid phase modification approaches for the formulation of APIs. Pharmaceutics, 2018, 10(1), 18.
[21]
Buddhadev, S.S.; Kevin, C. Garala, K.C. Pharmaceutical Cocrystals-A Review. Proceedings, 2020, 62, 14.
[http://dx.doi.org/10.3390/proceedings2020062014]
[22]
PubChem Saphris (Compounds). 2006. Available from: https://pubch0em.ncbi.nlm.nih.gov/compound/6917875
[23]
Mady, O. Studying the effect of dispersed drug crystal in the organic phase on the encapsulation by solvent evaporation technique (3) Independent models as tools for studying the drug release profiles. World J. Pharm. Sci., 2014, 2(4), 409-421.
[24]
In: Proceedings of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Q2 (R1). Geneva, Switzerland, November 1–13, 2005; Guideline IH. Validation of analytical procedures: text and methodology. 1(20): p. 05.
[25]
Al-Nimry, S.S.; Khanfar, M.S. Validation of an RP-HPLC method for the determination of asenapine maleate in dissolution media and application to study in vitro release from co-crystals. Sci. Pharm., 2021, 89, 14.
[http://dx.doi.org/10.3390/scipharm89010014]
[26]
Ramadan, N.K.; Mohamed, T.A.; Fouad, R.M.; Moustafa, A.A. Potentiometric determination of asenapine maleate using pvc membrane and carbon paste ion-selective electrodes. Organic & Medicinal Chem. IJ., 2018, 8(1), 555726 [OMCIJ].
[27]
Blatter, F.; Reichenbacher, K. Novel crystalline salts of asenapine with organic di-acids and tri-acids., US Patentts 9, 169, 262, 2015.
[28]
Saganowska, P.; Wesolowski, M. DSC as a screening tool for rapid co-crystal detection in binary mixtures of benzodiazepines with co-formers. J. Therm. Anal. Calorim., 2017, 133(1), 785-795.
[29]
Shewale, S.; Shete, A.S.; Doijad, R.C.; Kadam, S.S.; Patil, V.A.; Yadav, A.V. Formulation and solid state characterization of nicotinamide-based co-crystals of fenofibrate. Indian J. Pharm. Sci., 2015, 77(3), 328-334.
[30]
Chokshi, R.J.; Zia, H.; Sandhu, H.K.; Shah, N.H.; Malick, W.A. Improving the dissolution rate of poorly water soluble drug by solid dispersion and solid solution-pros and cons. Drug Deliv., 2007, 14(1), 33-45.
[31]
Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Drug Products Containing High Solubility Drug Substances. 2018. Available from: https://www.fda.gov/media/92988/download.
[32]
Kesisoglou, F.; Wu, Y. Understanding the effect of API properties on bioavailability through absorption modeling. The AAPS J., 2008, 10(4), 516-525.
[http://dx.doi.org/10.1208/s12248-008-9061-4]
[33]
Kurmi, R.; Mishra, D.K.; Jain, D.K. Solid dispersion: a novel means of solubility enhancement. J. Crit. Rev., 2016, 3(1), 1-8.
[34]
Wen, H.; Jung, H.; Li, X. Drug delivery approaches in addressing clinical pharmacology-related issues: opportunities and challenges. The AAPS J., 2015, 17(6), 1327-1340.

Rights & Permissions Print Cite
Article Metrics
30
1
© 2024 Bentham Science Publishers | Privacy Policy