CENTRAL COMPOSITE DESIGN FOR FORMULATION AND OPTIMIZATION OF LONG-ACTING INJECTABLE (LAI) MICROSPHERES OF PALIPERIDONE PALMITATE

Authors

  • SANDIP MALI Department of Pharmaceutical Science, Research, Development and Innovation Centre (RDIC), C. U. Shah University, Wadhwan City, Surendranagar 363030, Gujarat, India
  • NISHANT OZA Department of Pharmaceutical Science, Research, Development and Innovation Centre (RDIC), C. U. Shah University, Wadhwan City, Surendranagar 363030, Gujarat, India

DOI:

https://doi.org/10.22159/ijap.2021v13i5.42297

Keywords:

Central composite design, Face centered, PLGA, Long-acting, Injectable, Microspheres, Schizophrenia, Paliperidone palmitate

Abstract

Objective: The aim of the present study was to optimize long-acting injectable (LAI) microspheres of Paliperidone palmitate (PP) for treatment of schizophrenia using face-centered central composite design (FC-CCD).

Methods: In this study, poly lactic-co-glycolic acid (PLGA) based LAI microspheres of paliperidone palmitate (PP) were formulated by using FC-CCD. LAI microspheres were developed by using oil in water (O/W) emulsion solvent evaporation technique. On the basis of preliminary trials, FC-CCD was employed to check effect of independent variables such as drug polymer ratio (X1), homogenization speed (X2) and rate of addition (X3). While mean particle size (Y1), drug loading (Y2), entrapment efficiency (Y3), burst release (Y4), and drug release on day 60 (Y5) were considered as dependent variables and statistically evaluation performed by using design expert 12 software. Morphology of prepared microspheres was studied by using the scanning electron microscopy (SEM) technique, while particle size was analyzed by laser diffraction technique. In vitro drug release studies were performed using a controlled temperature shaking water bath apparatus. Fourier transforms infrared spectroscopy (FTIR) and differential scanning calorimetric (DSC) study were performed to analyze any changes in crystal behavior or to detect any chemical bonding between ingredients. 13C NMR and 1H NMR techniques were used to analyze end-capping and monomer ratio in developed microspheres.

Results: The factorial batches mean particle size was found to be 38 µm to 104 µm and drug loading were found between 27.2 % to 47.2%. Mathematical modelling of drug release kinetics revealed that near zero-order drug release of checkpoint formulations. Endcap analysis and molar ratio of formulated microspheres were found to be ester end cap and ~75:25, respectively. Morphologically all the prepared samples were found to be spherical in shape and smooth surface. FTIR data showed no significant interactions occurred between drug and excipients. The actual responses of checkpoint formulations were observed within 5% variation of predicted values.

Conclusion: The prepared microspheres showed promising results of morphology, particle size, drug loading, entrapment efficiency, burst release and drug release on day 60. The successful predictive designs models were achieved from employed FC-CCD.

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References

Saundersa EC, Mooreb SK, Walshb O, Metcalfb SA, Budneyb AJ, Schererb E, et al. Perceptions and preferences for long-acting injectable and implantable medications in comparison to short-acting medications for opioid use disorders. J Subst Abuse Treat 2020;111:54-66.

Lin CH, Chen FC, Chan HU, Hsu CC. A comparison of long-acting injectable antipsychotics with oral antipsychotics on time to rehospitalization within 1 y of discharge in elderly patients with schizophrenia. Am J Geriatric Psychiatry 2020;28:23-30.

Wei XL, Han YR, Quan LH, Liu CY, Liao YH. Oily nanosuspension for long-acting intramuscular delivery of curcumin didecanoate prodrug: preparation, characterization and in vivo evaluation. Eur J Pharm Sci 2013;49:286-93.

Kohli S, Pal A, Jain S. Preparation, characterization and evaluation of poly(Lactide-co-glycolide) microspheres for the controlled release of zidovudine. Int J Pharm Pharm Sci 2017;9:70-7.

Kar K, Pal RN, Bala NN. Preparation, characterization and evaluation of ropinirole hydrochloride loaded controlled release microspheres using solvent evaporation technique. Int J Pharm Pharm Sci 2018;10:57-67.

Nanaki S, Barmpalexis P, Papakonstantinou Z, Christodoulou E, Kostoglou M, Bikiaris DN. Preparation of new risperidone depot microspheres based on novel biocompatible poly (Alkylene Adipate) polyesters as long-acting injectable formulations. J Pharm Sci 2018;107:2891-901.

Mei L, Xie Y, Wang B, Chen J, Quan G, Pan X, et al. Injectable in situ forming gel based on lyotropic liquid crystal for persistent postoperative analgesia. Acta Biomater 2018;67:99-110.

Kamali H, Khodaverdi E, Hadizadeh F, Yazdian Robati R, Haghbin A, Zohuri G. An in-situ forming implant formulation of naltrexone with minimum initial burst release using a mixture of PLGA copolymers and ethyl heptanoate as an additive: In vitro, ex-vivo, and in vivo release evaluation. J Drug Delivery Sci Technol 2018;47:95-105.

He M, Yang G, Zhao X, Zhang S, Gao Y. Intradermal implantable PLGA microneedles for etonogestrel sustained release. J Pharm Sci 2010;109:1958-66.

Liua G, Zhanga D, Yang Jb, Guoa H, Zhenga D, Jia L, et al. In vitro and in vivo evaluation of riccardin D nanosuspensions with different particle size. Colloids Surf B 2013;102:620-6.

Fond G, Korchia T, Sunhary PL, Godin O, Schurhoff F, Berna F, et al. Major depression, sleep, hostility and body mass index are associated with impaired quality of life in schizophrenia. Results from the FACE-SZ cohort. J Affect Disord 2020;274:617-23.

Moller HJ. Antipsychotic agents. Gradually improving treatment from the traditional oral neuroleptics to the first atypical depot. Eur Psychiatry 2005;20:379-85.

Bloch Y, Mendlovic S, Strupinsky S, Altshuler A, Fennig S, Ratzoni G. Injections of depot antipsychotic medications in patients suffering from schizophrenia: do they hurt? J Clin Psychiatry 2001;62:855-9.

Csernansky JG, Mahmoud R, Bremer R. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med 2002;346:16-22.

Rubio JM, Schoretsanitis G, John M, Tiihonen J, Taipale H, Guinart D, et al. Psychosis relapse during treatment with long-acting injectable antipsychotics in individuals with schizophrenia-spectrum disorders: an individual participant data meta-analysis. Lancet Psychiatry 2020;7:749-61.

Correll CU, Rubio JM, Kane JM. What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry 2018;17:149-60.

Makadia HK, Siegel SJ. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers (Basel) 2011;3:1377-97.

Kapoor DN, Bhatia A, Kaur R, Sharma R, Kaur G, Dhawan S. PLGA: a unique polymer for drug delivery. Ther Delivery 2015;6:41-58.

Anderson JM, Shive MS. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Delivery Rev 1997;28:5-24.

Nussbaum AM, Stroup TS. Oral paliperidone for schizophrenia. Cochrane Database Syst Rev 2012;3:12-8.

Zacher JL. Paliperidone extended-release tablets (Invega). Psychopharmacol Rev 2007;42:51-8.

Freitas S, Merkle H, Gander B. Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microsphere preparation process technology. J Controlled Release 2005;102:313-32.

Garner J, Skidmore S, Park H, Park K, Choi S, Wang Y. Beyond Q1/Q2: the impact of manufacturing conditions and test methods on drug release from plga-based microparticle depot formulations. J Pharm Sci 2018;107:353-61.

Fang Y, Zhang N, Li Q, Chen J, Xiong S, Pan W. Characterizing the release mechanism of donepezil-loaded PLGA microspheres in vitro and in vivo. 2019;51:430-7.

Garner J, Skidmore S, Park H, Park K, Choi S, Wang Y. A protocol for assay of poly(lactide-co-glycolide) in clinical products. Int J Pharm 2015;495:87-92.

Dawes GJS, Fratila-Apachitei LE, Mulia K, Apachitei I, Witkamp GJ, Duszczyk J. Size effect of PLGA spheres on drug loading efficiency and release profiles. J Mater Sci Mater M 2009;20:1089-94.

Siegel SJ, Kahn JB, Metzger K, Winey KI, Werner K, Dan N. Effect of drug type on the degradation rate of PLGA matrices. Eur J Pharm Biopharm 2006;64:287-93.

Hillery A, Lloyd A, Swarbrick J. Drug delivery and targeting. London; New York, NY: Taylor and Francis Inc; 2005.

Derringer G, Suich R. Simultaneous optimization of several response variables. J Qual Technol 1980;12:214–9.

Iftikhar SY, Iqbal FM, Hassan W, Nasir B, Sarwar AR. Desirability combined response surface methodology approach for optimization of prednisolone acetate loaded chitosan nanoparticles and in vitro assessment. Mater Res Express 2020;7:1-10.

Published

07-09-2021

How to Cite

MALI, S., & OZA, N. (2021). CENTRAL COMPOSITE DESIGN FOR FORMULATION AND OPTIMIZATION OF LONG-ACTING INJECTABLE (LAI) MICROSPHERES OF PALIPERIDONE PALMITATE. International Journal of Applied Pharmaceutics, 13(5), 87–98. https://doi.org/10.22159/ijap.2021v13i5.42297

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