Preparation and characterization of an oral norethindrone sustained release/controlled release nanoparticles formulation based on chitosan

21^st Annual European Pharma Congress

May 20-22, 2019 | Zurich, Switzerland

Suhair S. Al-Nimry, Bashar M. Altaani, Razan H. Haddad and Rana Abu-Dahab

Jordan University of Science and Technology, Jordan
University of Jordan, Jordan

Posters & Accepted Abstracts: Pharmaceut Reg Affairs

Abstract :

Statement of the Problem: Norethindrone has short half-life and low bioavailability. The objective of this research was to prepare an oral Sustained Release/Controlled Release (SR/CR) Liquid Medicated Formulation (LMF) to enhance bioavailability and improve patient compliance. Methodology: Norethindrone was solubilized in HP-��- CD then complexed with different concentrations of Low Molecular Weight Chitosan (LMWC) (mucoadhesive). PolyElectrolyte Complexes (PECs) were homogenized with oleic acid using different concentrations of tween 80 to form LMFs (nanoemulsions). PECs and LMFs were characterized using DSC, FTIR spectroscopy and SEM images. Particle size, polydispersity index and zeta potential were measured. Dissolution studies were conducted and encapsulation efficiencies were calculated. LMF 2 (optimum formula containing 2.5% w/v LMWC 11 kDa) was administered orally to dogs and mice for pharmacokinetic and adhesion evaluation. Findings: DSC, FTIR spectroscopy and SEM images indicated complex formation. Mean diameters of PECs were 183â��425 nm, mean zeta potentials were + 18.6â��+ 31 mV, and complexation efficiencies were 18.0â��20.6%. Ten to fifteen percent tween 80 was needed to prepare homogenous LMFs. Mean diameter of LMF 2 was 10.5 �± 0.57 nm, mean zeta potential was â�� 11.07 �± â�� 0.49 mV, encapsulation efficiency was 95.28 �± 1.75%, and each mL contained 145.5 �¼ g norethindrone. SEM images showed spherical homogeneous oil droplets. All of these parameters were affected by molecular weight and concentration of chitosan. Norethindrone release from LMFs was controlled (zero order) for 96 h. It was little affected by molecular weight and concentration of chitosan but affected by concentration of tween 80. LMF 2 adhered to GIT for 48 h and enhanced the bioavailability. It showed no cytotoxicity after considering dilution in GIT and was stable for 3 months refrigerated. Conclusion & Significance: an effective SR/CR LMF for norethindrone was prepared.

Recent Publications

1. Suhair S. Al-Nimry, Bashar M. Altaani, Razan H. Haddad (2019) RP-HPLC method for determination of norethindrone in dissolution media and application to study release from a controlled release nanoparticulate liquid medicated formulation. J Appl Pharm Sci 9(02):079�086.

2. Bashar M. Altanni, Suhair S. Al-Nimry, Razan H. Haddad, Rana Abu-Dahab (2019) Preparation and Characterization of an Oral Norethindrone Sustained Release/Controlled Release Nanoparticles Formulation Based on Chitosan. AAPS PharmSciTech 7;20(2):54.

3. Suhair Al-Nimry, Khouloud Alkhamis (2018) Effect of Moisture Content of Chitin-Calcium Silicate on Rate of Degradation of Cefotaxime Sodium. AAPS PharmSciTech 19(3):1337-1343.

4. Mai Khanfar, Suhair Al-Nimry (2017) Stabilization and amorphization of lovastatin using different types of silica. AAPS PharmSciTech 18(6):2358-2367.

5. Suhair S. Al-Nimry, Malak A. Jaber (2017) Development and validation of an HPLC-UV method for determination of sertraline hydrochloride and application to study dissolution of tablets. Latin American Journal of Pharmacy 36 (4): 665-72.

6. Suhair Al-Nimry, Khouloud Alkhamis, Kawthar Alzarieni (2017) The effect of specific surface area of chitinmetal silicate coprocessed excipient on the chemical decomposition of cefotaxime sodium. J Pharm Sci 106:570- 578.

7. Suhair S. Al-Nimry, Malak A. Jaber (2017) Preparation and Optimization of Sertraline Hydrochloride Tablets with Improved Dissolution through Crystal Modification. AAPS PharmSciTech 18(4):1190-1202.

Biography :