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Development and Evaluation of pH-Responsive Cyclodextrin-Based in situ Gel of Paliperidone for Intranasal Delivery

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Abstract

Paliperidone (PLPD) is approved for treatment and management of schizophrenia. The current study demonstrates the potential of in situ gel of PLPD for nasal delivery. The permeation of drug through sheep nasal mucosa was analyzed since the nose-to-brain pathway has been indicated for delivering drugs to the brain. The carbopol 934 (CP)- and hydroxypropyl methyl cellulose K4M (HPMC)-based in situ gels containing 0.2% CP and 0.4% w/v HPMC were optimized using experimental design software. The use of hydroxypropyl-β-cyclodextrin (HP-β-CD) in nasal permeation of drug was investigated. Transmucosal permeation of PLPD was examined using sheep nasal mucosa. The in situ gels of PLPD exhibited satisfactory mucoadhesion and showed sustained drug release. The mucocilliary toxicity and histopathological examination confirmed that the nasal mucosa architecture remains unaffected after treatment with PLPD in situ gel. The formulation containing HP-β-CD complex of PLPD exhibited higher rate of drug permeation through sheep nasal mucosa revealing the role of HP-β-CD as nasal absorption enhancer. Thus, CP- and HPMC-based pH-triggered in situ gel containing HP-β-CD-drug inclusion complex demonstrates a novel nasal delivery of PLPD.

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Acknowledgements

The authors are thankful to Cadila Pharmaceuticals Ltd., India, and Gangwal Chemicals Pvt. Ltd., India, for providing gift samples of paliperidone and HP-β-CD, respectively.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry & Quality Assurance, SVKM’s Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, 400056, India

    Atul P. Sherje

  2. Department of Pharmaceutics, SPP School of Pharmacy & Technology Management, SVKM’s NMIMS, Vile Parle (W), Mumbai, 400056, India

    Vaishali Londhe

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Correspondence to Atul P. Sherje.

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Sherje, A.P., Londhe, V. Development and Evaluation of pH-Responsive Cyclodextrin-Based in situ Gel of Paliperidone for Intranasal Delivery. AAPS PharmSciTech 19, 384–394 (2018). https://doi.org/10.1208/s12249-017-0844-8

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