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Influence of hydrophilic polymers addition into cinnarizine–β-cyclodextrin complexes on drug solubility, drug liberation behaviour and drug permeability

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Abstract

The aims of this study were (1) to prepare cinnarizine (CNZ)–β-cyclodextrin (β-CD) complexes by the kneading, co-precipitation and co-evaporation methods with (ternary system) or without (binary system) the addition of two different hydrophilic polymers [hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP)] in their two different grades (HPMC E5-LV or K4M and PVP K-25 or K-30) and (2) to determine the polymers influence on enhancing the CNZ solubility and the in vitro CNZ liberation behaviour or drug permeation characteristics via artificial membrane from the prepared CNZ–β-CD binary and ternary complexes in 0.1 N HCl (pH 1.2). The presence of hydrophilic polymers in ternary complex system did produce irregular-shaped but smooth-surfaced particles while binary complex system (with no polymer addition) did not. The ternary complexes prepared with HPMC K4M, β-CD and CNZ showed higher solubility efficiency value compared to other tested hydrophilic polymers to make ternary complex systems. Consequently, irrespective of the three preparation methods, the ternary complex systems exhibited higher drug libration behaviour in comparison to the binary complex system, physical mixtures and CNZ powder. But because of the possible presence of a solubility and permeability interplay or tradeoff particularly in the binary and ternary complex systems, the CNZ permeation amount in 0.1 N HCl (pH 1.2) via artificial membrane was established to a minimum compared to the CNZ powder. Therefore, the CNZ–β-CD complexes with or without the HPMC and PVP should unequivocally be used with great care by considering the solubility–permeability interplay or tradeoff into account.

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Acknowledgements

The encouragement and support given by the management of Lovely Professional University, India, to perform this research work is acknowledged.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi, G.T. Road (NH-1), Phagwara, Jalandhar, Punjab, 144411, India

    Harmanpreet Singh, Manish Kumar, Suksham Gupta & Shunmugaperumal Tamilvanan

  2. Department of Pharmaceutics, Sankaralingam Bhuvaneswari College of Pharmacy, Sivakasi, Tamil Nadu, India

    Thenrajan Raja Sekharan

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  1. Harmanpreet Singh
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289_2017_2203_MOESM1_ESM.jpg

Supplementary Fig. 1. Thermograms obtained by differential scanning calorimetry (A) cinnarizine (CNZ), (B) β-cyclodextrin (β-CD), (C) HPMC K4M, (D) Physical mixture of ternary complexes made using HPMC K4M, β-CD and CNZ, (E) Ternary complexes prepared by Kneading method, (F) Ternary complexes made by co-precipitation method (Mid-point melting temperature and fusion enthalpy values are shown in Table 4) 1 (JPEG 250 kb)

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Singh, H., Kumar, M., Gupta, S. et al. Influence of hydrophilic polymers addition into cinnarizine–β-cyclodextrin complexes on drug solubility, drug liberation behaviour and drug permeability. Polym. Bull. 75, 2987–3009 (2018). https://doi.org/10.1007/s00289-017-2203-z

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