A QBD WITH THE FRACTIONAL FACTORIAL DESIGN WAS USED TO MATCH THE SIMILARITY BETWEEN RANOLAZINE EXTENDED-RELEASE TABLETS 500 MG AND 1000 MG

SANKARAIAH JONNA; HANIMI REDDY BAPATU; PRAVEEN SUBBAPPA; KALIYAPERUMAL SARAVANAN

doi:10.22159/ijap.2023v15i2.47241

Authors

SANKARAIAH JONNA Department of Pharmaceutics, Bhagwant University, Ajmer, Rajasthan, India
HANIMI REDDY BAPATU Department of Chemistry, JNT University, Kukatpally, Hyderabad, Telangana, India
PRAVEEN SUBBAPPA Government College of Pharmacy, Rajiv Gandhi university of Health Sciences, Bangalore, India
KALIYAPERUMAL SARAVANAN Faculty of Pharmacy, Bhagwant University, Ajmer, Rajasthan, India https://orcid.org/0000-0002-8859-8099

DOI:

https://doi.org/10.22159/ijap.2023v15i2.47241

Keywords:

Ranolazine, Extended-release tablets, DOE, QbD, Fractional factorial design, Design expert

Abstract

Objective: Formulation and development of Ranolazine extended-release Tablets 500 mg and 1000 mg by using QBD with Fractional factorial design to match the similarity with Branded formulation (RANEXA®).

Methods: Ranolazine extended-release tablets were developed by using various polymers, Polyquid PA100 and ETHOCEL ^TMstandard 7 premium and Hypromellose with a wet granulation process. QBD (Quality by Design) approach was used to identify the formulation and process variables that may affect the CQAs (critical quality attributes). Excipient compatibility studies were conducted to identify the interaction between API (active pharmaceutical ingredient) and selected excipients. Additionally, using a two-level, fractional factorial (2²+3) design, the DOE (design of experiments) was employed to confirm the impacts of key process factors (fluid uptake and kneading time) on the formulation's ability to match the dissolution (f2) compared to RLD (reference listed drug) and establish a stable formulation.

Results: Initial risk assessment was carried out to identify the various attributes such as API flow properties, solubility, PSD, Hygroscopicity, formulation, and process variables to impact the quality of the drug product. Flow properties of API indicate poor flow. Drug and excipients compatible study results indicate that excipients used in the compatibility study are considered compatible with the active ingredient. As per the saturation solubility studies and sink conditions, dissolution media was selected. Significant differences were found among the drug release profile by examining the various levels of polymers and binders. Using a two-level, fractional factorial (2²+3) design, optimum process parameters were identified with selected formulation to match the dissolution (f2) similarity with the reference listed drug (RLD); finally, XRD (X-ray diffraction) studies confirm that the crystalline polymorphic forms (Form 1) peaks in optimum formulation (F07) comparable to the reference listed drug.

Conclusion: Optimized formulation and process were established with QbD (quality by design) that provides the consistent drug release to match the f2 similarities with the extended-release tablets of RANEXA^®(Ranolazine) 500 mg and 1000 mg.

Downloads

Download data is not yet available.

References

Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation. 2006;113(20):2462-72. doi: 10.1161/CIRCULATIONAHA.105.597500. PMID 16717165.

McCormack JG, Barr RL, Wolff AA, Lopaschuk GD. Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts. Circulation. 1996;93(1):135-42. doi: 10.1161/01.cir.93.1.135. PMID 8616920.

Chaitman BR, Skettino SL, Parker JO, Hanley P, Meluzin J, Kuch J. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004;43(8):1375-82. doi: 10.1016/j.jacc.2003.11.045. PMID 15093870.

Leelapatana P, Thongprayoon C, Prasitlumkum N, Vallabhajosyula S, Cheungpasitporn W, Chokesuwattanaskul R. Role of ranolazine in the prevention and treatment of atrial fibrillation in patients with left ventricular systolic dysfunction: A meta-analysis of randomized clinical trials. Diseases. 2021;9(2):31. doi: 10.3390/ diseases9020031, PMID 33923428.

Bhandari B, Subramanian L. Ranolazine, a partial fatty acid oxidation inhibitor, its potential benefit in angina and other cardiovascular disorders. Recent Pat Cardiovasc Drug Discov. 2007;2(1):35-9. doi: 10.2174/157489007779606095, PMID 18221101.

Calcagno S, Infusino F, Salvi N, Taccheri T, Colantonio R, Bruno E. The role of ranolazine for the treatment of residual angina beyond the percutaneous coronary revascularization. J Clin Med. 2020;9(7):2110. doi: 10.3390/jcm9072110, PMID 32635532.

Siddiqui MAA, Keam SJ. Ranolazine: a review of its use in chronic stable angina pectoris. Drugs. 2006;66(5):693-710. doi: 10.2165/00003495-200666050-00010, PMID 16620147.

Salazar CA, Basilio Flores JE, Veramendi Espinoza LE, Mejia Dolores JW, Rey Rodriguez DE, Loza Munarriz C. Ranolazine for stable angina pectoris. Cochrane Database Syst Rev. 2017;2(2):CD011747. doi: 10.1002/14651858.CD011747. pub2. PMID 28178363.

Bose A, Wong TW, Singh N. Formulation development and optimization of sustained release matrix tablet of itopride HCl by response surface methodology and its evaluation of release kinetics. Saudi Pharm J. 2013;21(2):201-13. doi: 10.1016/j.jsps.2012.03.006. PMID 23960836.

Swain S. Responsibility of regulatory affairs in pharmaceutical industry. Pharmaceut Reg Affairs. 2022;01(1). doi: 10.4172/2167-7689.1000104.

Nair AK. MU impact of API (Active pharmaceutical ingredient) source selection on generic drug products. Pharmaceut Reg Affairs 2015;04(2). doi: 10.4172/2167-7689.1000136.

Khajavi F. Formulation of extended-release ranolazine tablet and investigation of its stability in the accelerated stability condition at 40 ⁰C and 75 % humidity. J Pharma Res Rep. 2021;2:1-3. doi: 10.47363/JPRSR/2021(2)106.

Nair AK, Ramana PV, Rao PVB, Reddy BH, Ganthi HKR, Mallu UR. Carobomer-based controlled release designs of atorvastatin calcium tablets were evaluated using the quality by design (QbD) approach. Am J Anal Chem. 2017;08(3):189-209. doi: 10.4236/ajac.2017.83016.

Bapatu HR, Maram RK, Cho WH, Pasagadugula VBR. QbD approach method development for estimation of dabigatran etexilate along with its impurities and identification of degradants in the capsule dosage form. Am J Anal Chem. 2016;07(6):494-524. doi: 10.4236/ajac.2016.76047.

Mofizur Rahman Md. Formulation and evaluation of ranolazine sustained release matrix tablets using Eudragit and HPMC. Int J Pharm Biomed Res. 2011;1(5):172-7.

Mofizur Rahman Md. Effect of various grades of hydroxy propyl methyl cellulose matrix systems as oral sustained release drug delivery systems for ranolazine. IJPI’s J Pharm Cosmetol. 2011;1:2.

Gunda RK, Manchineni PR, Duraiswamy D, Gsn KR. Design, development, optimization and evaluation of ranolazine extended-release tablets. Turk J Pharm Sci. 2022;19(2):125-31. doi: 10.4274/tjps.galenos.2021.58047. PMID 35509223.

Murthy T, Babu V, Mukkala BV. Formulation and evaluation of ranolazine extended-release tablets: influence of polymers. Asian J Pharm. 2011;5(3). doi: 10.4103/0973-8398.91992.

Abdelbary A, El-Gazayerly ON, El-Gendy NA, Ali AA. Floating tablet of trimetazidine dihydrochloride: an approach for extended-release with zero-order kinetics. AAPS PharmSciTech. 2010;11(3):1058-67. doi: 10.1208/s12249-010-9468-y, PMID 20582493.

Deepika D. Formulation and evaluation of film-coated ranolazine sustained release matrix tablets. Int J Appl. 2015;2(5):38-53.

Kumari MV, Reddy PV, Sudhakar M. Formulation and evaluation of sustained release matrix tablets of ranolazine. Int J Pharm. 2012;2(1):224-9.

Evin Aycicek D. Stability indicating method development and validation of ranolazine extended-release tablets acta. Pharm Sci. 2021;59(3):05925. doi: 10.23893/1307-2080.

Swain S, Parhi R, Jena BR, Babu SM. Quality by design: concept to applications. Curr Drug Discov Technol. 2019;16(3):240-50. doi: 10.2174/1570163815666180308142016, PMID 29521238.

Chappidi SR, Bhargav E, Marikunte V, Chinthaginjala H, Vijaya Jyothi M, Pisay M. A cost-effective (QbD) approach in the development and optimization of rosiglitazone maleate mucoadhesive extended release tablets-in vitro and ex vivo. Adv Pharm Bull. 2019;9(2):281-8. doi: 10.15171/apb.2019.032, PMID 31380254.

Chudiwal VS, Shahi S, Chudiwal S. Development of sustained release gastro-retentive tablet formulation of nicardipine hydrochloride using quality by design (QbD) approach. Drug Dev Ind Pharm. 2018;44(5):787-99. doi: 10.1080/03639045.2017.1413111, PMID 29198152.

Politis NS, Colombo P, Colombo G, M Rekkas D. Design of experiments (DoE) in pharmaceutical development. Drug Dev Ind Pharm. 2017;43(6):889-901. doi: 10.1080/ 03639045.2017.1291672.

Shah V, Khambhla E, Nivsarkar M, Trivedi R, Patel RK. An integrative QbD approach for the development and optimization of controlled release compressed coated formulation of water-soluble drugs. AAPS PharmSciTech. 2022;23(5):120. doi: 10.1208/s12249-022-02225-9, PMID 35460024.

Bose A, Wong TW, Singh N. Formulation development and optimization of sustained release matrix tablet of itopride HCl by response surface methodology and its evaluation of release kinetics. Saudi Pharm J. 2013;21(2):201-13. doi: 10.1016/j.jsps.2012.03.006. PMID 23960836.

Saravanakumar M, Venkateswaramurthy N, Dhachinamoorthi D, Perumal P. Extended release matrix tablets of stavudine: formulation and in vitro evaluation. Asian J Pharm. 2010;4(3):219-23. doi: 10.4103/0973-8398.72122.

Sangshetti JN, Deshpande M, Zaheer Z, Shinde DB, Arote R. Quality by design approach: regulatory need. Arab J Chem. 2017;10:S3412-25. doi: 10.1016/j.arabjc.2014.01.025. arabjc.2014.01.025.

Ha JM, Seo JW, Kim SH, Kim JY, Park CW, Rhee YS. Implementation of quality by design for the formulation of rebamipide gastro-retentive tablet. AAPS PharmSciTech. 2017 Nov;18(8):3129-39. doi: 10.1208/s12249-017-0797-y, PMID 28526986.

Sankaraiah J, Sharma N, Naim MJ. Formulation and evaluation of the fixed-dose combination of bilayer tablets of atazanavir sulfate and ritonavir 300 mg/100 mg. Int J App Pharm. 2021;13:60-72. doi: 10.22159/ijap.2021v13i5.41860.

Sankaraiah J, Sharma N, Naim MJ. Formulation and development of the fixed-dose combination of bi-layer tablets of efavirenz, lamivudine and tenofovir disoproxil fumarate tablets 600 MG/300 MG/300 MG. Int J App Pharm. 2022;14:185-97. doi: 10.22159/ijap.2022v14i1.42764.

Bapatu HR, Maram RK, Cho WH, Pasagadugula VBR. QbD approach method development for estimation of dabigatran etexilate along with its impurities and identification of degradants in capsule dosage form. Am J Anal Chem. 2016;07(6):494-524. doi: 10.4236/ajac.2016.76047.

Bharathi Arigela, Nikitha Ponnam, Poojitha Chimata, Haritha Mandava, Chandra Sekhar Naik D. Formulation and evaluation of ranolazine extended-release tablets. Indo-American Journal of Pharmaceutical Sciences. 2018;05(07):6445-53. https://doi.org/10.5281/zenodo.1311884.

Sopyan I, Gozali D, Sriwidodo, Guntina RK. Design-expert software (DOE): an application tool for optimization in pharmaceutical preparations formulation. International Journal of Applied Pharmaceutics. 2022;14(4):55-63.

Sagar S, Srinivas L. Development and evaluation of raft forming gastro retentive floating drug delivery system of nizatidine by the design of experiment. Int J App Pharm. 2022;14(2):242-51. https://doi.org/10.22159/ijap.2022v14i2.