Polyvinyl Polymer- Based Olanzapine Nanoparticles for Transdermal Delivery: Design, In-vitro and Ex-vivo Evaluation
DOI:
https://doi.org/10.31351/vol33iss(4SI)pp119-132Keywords:
Olanzapine, Solubility, PVP-K15, Nanoparticles, NanoprecipitationAbstract
Abstract
Olanzapine (OLZ) is classified a typical antipsychotic drug, which utilized for treatment of schizophrenia. It possesses poor water solubility and high membrane permeability, so, OLZ classified as class II according to biopharmaceutical classification system (BCS). Its oral bioavailability is (60%) due to poor solubility and extensive first-pass hepatic metabolism. Hence, the objective of this study was to prepare and evaluate the nanoparticles of OLZ for transdermal delivery. Nanoprecipitation method was employed to formulate the nanoparticles, where methanol utilized to dissolve the drug and form organic phase, which was added to an aqueous phase that consist of deionized water and stabilizer at speed of 1ml/min using syringe pump. The formulations of nanoparticles were evaluated by different characterization studies like particle size determination, polydispersity index (PDI), zeta potential, entrapment efficiency and an in vitro release of drug in order to select the optimized formula. The optimized formula was subjected for further studies such as surface morphology by field emission scanning electron microscope (FESEM) and atomic force microscope (AFM), fourier transform infrared spectroscopy (FTIR) to investigate the compatibility between drug and polymer and differential scanning calorimetry (DSC). The results of characterizations revealed that OLZ nanoparticle (OLZ-8) is selected as optimized formula, which consist of polyvinylpyrrolidone (PVP-K15) and OLZ in ratio (2:1). The characteristics of OLZ-8 were mean particle size (95.2±4.66 nm), PDI (0.282±0.18), zeta potential (-17.09 mV), entrapment efficiency (76.4±6.93) and an in vitro release of drug was higher and significant (P<0.05) as compared with other formulations and pure drug. FESEM and AFM revealed that the morphology of nanoparticle OLZ-8 was spherical in shape, also, AFM revealed that the particle size of OLZ-8 is approximate to the size that recorded by zeta sizer. FTIR studies revealed that there was a compatibility between drug and polymer. DSC results indicated that there was a decrease in crystallinity of OLZ. It can be concluded that the optimized formula OLZ-8 was regarded as a promising formula to improve the bioavailability of olanzapine when prepared as dissolving microneedle for transdermal delivery in future.
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Alaa A. Abdulqader, Eman B.H. Al-Khedairy. Formulation and evaluation of fast dissolving tablets of taste-masked ondansetron hydrochloride by solid dispersion. Iraqi J Pharm Sci.2017;26(1):50-60.
Homayun B, Lin X, Choi HJ. Challenges and recent progress in oral drug delivery systems for biopharmaceuticals. Pharmaceutics. 2019; 11(3):129.
Kanupriya C, Seth N, Gill NS. Gastro Retentive Drug Delivery System: A significant tool to increase the gastric residence time of drugs. Int. J. Curr. Pharm. Res. 2021: 7-11.
Shivakalyani Adepu, Seeram Ramakrishna. Controlled Drug Delivery Systems: Current Status and Future Directions. Molecules. 2021; 26:5905.
Won Fen Wong, Kuan Ping Ang, Gautam Sethi, Chung Yeng Looi. Recent Advancement of Medical Patch for Transdermal Drug Delivery. Medicina.2023; 59:778.
Zainab Ahmed Sadeq, Nawal A. Rajab, Shaimaa N. Abd Alhammid, Hiba Zaki. Preparation, in-vitro evaluation, mechanical characterization, and release of nebivelol hydrochloride as a transdermal film using combined eudragite-polyvinyl alcohol as adhesive film forming polymer. J. Pharm. Sci. Res. 2019; 11(3):1052-1055.
Singh R, Lillard JW Jr. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009;86(3):215-23.
Szczęch M., Szczepanowicz K. Polymeric Core-Shell Nanoparticles Prepared by Spontaneous Emulsification Solvent Evaporation and Functionalized by the Layer-by-Layer Method. Nanomaterials. 2020; 10:496.
Kolli P, Kelley G, Rosales M, Faden J, Serdenes R. Olanzapine Pharmacokinetics: A Clinical Review of Current Insights and Remaining Questions. Pharmgenomics Pers Med. 2023; 16:1097-1108.
Amidon GL, Lennernas. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res.1995;( 12): 413-20.
Somayeh Jafari, Francesca Fernandez-Enright, Xu-Feng Huang. Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects. J. Neurochem. 2012; 120:371–384.
Al-Shaibani AJN, Ghareeb MM. Preparation and optimization of olanzapine as transdermal nanoparticles delivery dystem. Al-Rafidain J Med Sci. 2024;6(2):76-81.
Rusul M. Alwan, Nawal A. Rajab. Nanosuspensions of Selexipag: Formulation, Characterization, and in vitro Evaluation. Iraqi J Pharm Sci.2021;30(1):144-153.
Alhagiesa AW, Ghareeb MM. Formulation and evaluation of Nimodipine Nanoparticles incorporated within Orodispersible tablets. IJDDT. 2020;10(4):547-552.
Hamed HE, A. Hussein A. Preparation, in vitro and ex-vivo Evaluation of Mirtazapine Nanosuspension and Nanoparticles Incorporated in Orodispersible Tablets. Iraqi J Pharm Sci. 2020;29(1):62–75.
Sreelola V, Sailaja AK, Pharmacy M. Preparation and characterisation of ibuprofen loaded polymeric nanoparticles by solvent evaporation technique. Int J Pharm Pharm Sci. 2014;6(8):416-21.
Hasanain Sh. Mahmood, Mowafaq M. Ghareeb, Zahraa Oleiwi Hamzah. Formulation and In-Vitro Evaluation of Flurbiprofen Nanoparticles for Transdermal Delivery. J Complement Med Res. 2020;11(5):223.
J. Joysa Ruby, V. P. Pandey. Formulation and evaluation of olanzapine loaded chitosan nanoparticles for nose to brain targeting an in vitro and ex vivo toxicity study. J. Appl. Pharm. Sci. 2016; 6 (09): 034-040.
Sameer V. Dalvi, Rajesh N. Dave. Controlling particle size of a poorly water-soluble drug using ultrasound and stabilizers in antisolvent precipitation. Ind. Eng. Chem. Res.2009;48(16):7581-7593.
Emil Joseph, Garima Balwani, Vibhu Nagpal, Satish Reddi. Validated UV Spectrophotometric Methods for the Estimation of Olanzapine in Bulk, Pharmaceutical Formulations and Preformulation Studies. BJPR.2015;6(3):180-190.
Kamnev AA, Dyatlova YA, Kenzhegulov OA. Fourier Transform Infrared (FTIR) Spectroscopic Analyses of Microbiological Samples and Biogenic Selenium Nanoparticles of Microbial Origin: Sample Preparation Effects. Molecules. 2021; 26(4):1146.
Antunes. Determination of the melting temperature, heat of fusion, and purity analysis of different samples of zidovudine using DSC. Braz. J. Pharm. Sci. 2010;46(1):38-43.
Nawal A. Rajab, Mohammad S. Jawad. Formulation and in vitro evaluation of piroxicam microsponge as a tablet. Int J Pharm Pharm Sci,2015; 8(2):104-114.
Kamil K. Atiyah Altameemi, Shaimaa N. Abd-Alhammid. Anastrozole Nanoparticles for transdermal Delivery through microneedles: Preparation and evaluation. J PHARM NEGATIVE RESULTS. 2022; 13:974-980.
Hayder Kadhim Drais, Ahmed Abbas Hussein. Investigation of lipid polymer hybrid nanocarriers for oral felodipine delivery: Formulation, method, in-vitro and ex-vivo evaluation. Iraqi J Pharm ScI.2022;31(1):119-129.
Rawaa M. Hussien, Mowafaq M. Ghareeb. Formulation and Characterization of Isradipine Nanoparticle for Dissolution Enhancement. Iraqi J Pharm Sci.2021;30(1):218-225.
Danaei M, Dehghankhold M, Ataei S. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics. 2018;10(2):57.
Liu D, Xu H, Tian B, Yuan K, Pan H, Ma S. Fabrication of carvedilol nanosuspensions through the anti-solvent precipitation-ultrasonication method for the improvement of dissolution rate and oral bioavailability. AAPS Pharm SciTech. 2012;13(1):295-304.
Rohit Mishra, Showkat R Mir, Saima Amin. Polymeric Nanoparticles for Improved Bioavailability of Cilnidipine. Int J Pharm Pharm Sci, 2017;9(4):129-139.
Fatimah M. Hussein Wais, Ahmed N. Abood and Hayder K. Abbas. Preparation and Evaluation of Ketoprofen Nanosuspension Using Solvent Evaporation Technique. Iraqi J Pharm Sci.2017;26(2): 41-55.
Muneer R, Hashmet M.R, Pourafshary P. DLVO Modeling to Predict Critical Salt Concentration to Initiate Fines Migration Pre-and Post-Nano fluid Treatment in Sandstones. SPE J. 2022; 27:1915-1929.
Nawal Ayash Rajab, Nizar Awish Jassem. A Design and in vitro evaluation of azilsartan medoxomil as a self-dispersible dry nanosuspension. Der Pharmacia Sinica. 2018; 9(1):12-322.
Ismanelly Hanum T, Nasution A, Sumaiyah S, Bangun H. Physical stability and dissolution of ketoprofen nanosuspension formulation: Polyvinylpyrrolidone and Tween 80 as stabilizers. Pharmacia.2023;70(1):209-215.
Salatin S, Barar J, Barzegar-Jalali M. Development of a nanoprecipitation method for the entrapment of a very water soluble drug into Eudragit RL nanoparticles. Res Pharm Sci. 2017;12(1):1-14.
Aparna Ashok chavan, Amol Somanath Shete, Bhagyesh Uttamrao Janugade. Formulation, Solid State Characterization and Enhancement of Dissolution Rate of Olmesartan Medoxomil by Polyvinyl Alcohol-Polyethylene Glycol Graft Copolymer Based Nanoparticles. Indian J. Pharm. Educ. Res.2016; 50(4):677-688.
Prasenjit Sarkar, Saumyajyoti Das, Sutapa Biswas Majee. Solid dispersion Tablets in Improving Oral Bioavailability of poorly soluble drugs. Int J Curr Pharm Res.2022;14(2):15-20.
Kallum M. Koczkur, Stefanos Mourdikoudis, Lakshminarayana Polavarapu, Sara E. Skrabalak. Polyvinylpyrrolidone (PVP) in nanoparticle synthesis. Dalton Transactions. 2015; 44 (41):17883-17905.
Ajit Shankarrao K, Dhairysheel Mahadeo G, Pankaj Balavantrao K. Formulation and In-vitro Evaluation of Orally Disintegrating Tablets of Olanzapine-2-Hydroxypropyl-β-Cyclodextrin Inclusion Complex. Iran J Pharm Res. 2010;9(4):335-47.
Shashi Ravi Suman Rudrangi, Vivek Trivedi, John C Mitchell, Stephen Richard Wicks, Bruce David Alexander. Preparation of olanzapine and methyl--cyclodextrin complexes using a single-step, organic solvent-free supercritical fluid process: An approach to enhance the solubility and dissolution properties. IJPR. 2015;494(1):408-16.
Venkateskumar Krishnamoorthy, Suchandrasen, Verma Priya Ranjan Prasad. Physicochemical characterization and in vitro dissolution behavior of olanzapine-mannitol solid dispersions. BJPS.2012;48(2): 244-255.
Krishnamoorthy V, Nagalingam A, Priya Ranjan Prasad V, Parameshwaran S, George N, Kaliyan P. Characterization of olanzapine-solid dispersions. Iran J Pharm Res. 2011;10(1):13-24.
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