Optimizing irbesartan spherical agglomerates through principal component analysis and experimental design

V. D.  Gorde; Punit R.  Rachh; S. D.  Mankar; Saurin Amin

doi:10.69857/joapr.v12i3.581

Authors

V. D. Gorde Department of Pharmaceutical Science, Bhagwant University, Ajmer, Rajasthan, India
Punit R. Rachh Department of Pharmaceutical Science, Bhagwant University, Ajmer, Rajasthan, India
S. D. Mankar Pravara Rural College of Pharmacy, Loni, Maharastra, India
Saurin Amin Gujarat Technological University, Gujarat, India

DOI:

https://doi.org/10.69857/joapr.v12i3.581

Keywords:

Central composite design, Packing and compaction, Flow property, Kawakita analysis, Principal component analysis

Abstract

Background: This study explores the amalgamation of crystallization and agglomeration through spherical crystallization, aiming to develop the spherical crystals of Irbesartan with improved micromeritic properties. The main objective is to use spherical crystallization techniques to improve the micromeritic characteristics of Irbesartan, which has poor flow and compressibility because of its crystal habit. Methodology: A solvent change approach was utilized to synthesize spherical agglomerates of Irbesartan. Several system parameters, including the amount of bridging liquid, the rate of stirring, and the concentration of the polymer, were tuned to enhance the particle size distribution and mechanical qualities. SEM, GC, PXRD, DSC, and FTIR analyses characterised the spherical crystals. Result and Discussion: The study demonstrated that spherical crystallization significantly enhanced Irbesartan's micromeritic properties. The angle of repose of optimized agglomerates was reduced by around 52%, indicating improved considerably flowability of irbesartan. The sphericity of the crystals was validated by SEM examination (shape factor: 0.996), and the solvent levels were found to be within allowable bounds by GC analysis. PXRD data showed no polymorphism alterations, and DSC/FTIR analyses confirmed that the excipients and drug were compatible. Conclusion: This process provides a feasible alternative to classic granulation and agglomeration procedures, resulting in better flow, compressibility, and spherical crystals. It streamlines the Irbesartan formulation, improving efficiency and uniformity, reducing manufacturing costs, higher tablet consistency, and enhancing patient compliance.

Downloads

Download data is not yet available.

References

Arabi JH, Subramanian L, Rajesh M. A review on spherical crystallization: a novel technique in the field of particle engineering. World Journal of Biology Pharmacy and Health Sciences, 13(1), 78–93 (2023).

Kawashima Y. Development of spherical crystallization technique and its application to pharmaceutical systems. Archives of Pharmacal Research, 7(2), 145–151 (1984).

Garala KC, Patel JM, Dhingani AP, Dharamsi AT. Preparation and evaluation of agglomerated crystals by crystallo-co-agglomeration: an integrated approach of principal component analysis and Box–Behnken experimental design. International Journal of Pharmaceutics, 452(1–2), 135–156 (2013).

Shangraw RF. Compressed tablets by direct compression. Pharmaceutical Dosage Forms: Tablets, 1, 195–246 (1989).

Garala KC, Patel JM, Dhingani AP, Dharamsi AT. Quality by design (QbD) approach for developing agglomerates containing racecadotril and loperamide hydrochloride by crystallo-co-agglomeration. Powder Technology, 247, 128–146 (2013).

Chattoraj S, Sun CC. Crystal and particle engineering strategies for improving powder compression and flow properties to enable continuous tablet manufacturing by direct compression. Journal of Pharmaceutical Sciences, 107(4), 968–974 (2018).

Rojas J, Buckner I, Kumar V. Co-processed excipients with enhanced direct compression functionality for improved tableting performance. Drug Development and Industrial Pharmacy, 38(10), 1159–1170 (2012).

Mohan S. Compression physics of pharmaceutical powders: a review. International Journal of Pharmaceutical Sciences and Research, 3(6), 1580–1592 (2012).

Negro R. Endothelial effects of antihypertensive treatment: focus on irbesartan. Vascular Health and Risk Management, 4(1), 89 (2008).

Pangarkar P, Thenge R, Mahajan N, Adhao V, Ajmire P. Crystal modification of irbesartan in presence of additive. Journal of Advanced Pharmacy Education & Research, 4(1), 106 – 113 (2014).

Patel J, Dhingani A, Garala K, Raval M, Sheth N. Quality by design approach for oral bioavailability enhancement of irbesartan by self-nanoemulsifying tablets. Drug Delivery, 21(6), 412–435 (2014).

Katta J, Rasmuson ÅC. Spherical crystallization of benzoic acid. International Journal of Pharmaceutics, 348(1–2), 61–69 (2008).

Garala K, Joshi P, Shah M, Ramkishan A, Patel J. Formulation and evaluation of periodontal in situ gel. International Journal of Pharmaceutical Investigation, 3(1), 29 (2013).

Raval MK, Garala KC, Patel JM, Parikh RK, Sheth NR. Functionality improvement of Chlorzoxazone by crystallo-co-agglomeration using multivariate analysis approach. Particulate Science and Technology, 39(6), 689–711 (2021).

Davidson MW, Abramowitz M. Optical microscopy. Encyclopedia of Imaging Science and Technology, 2 (1106–1141), 120 (2002).

Islam SF, Hawkins SM, Meyer JL, Sharman AR. Evaluation of different particle size distribution and morphology characterization techniques. Additive Manufacturing Letters, 3, 100077 (2022).

Al-Hashemi HMB, Al-Amoudi OSB. A review on the angle of repose of granular materials. Powder Technology, 330, 397–417 (2018).

Tapas A, Kawtikwar P, Sakarkar D. An improvement of micromeritic properties and dissolution behaviors of carvedilol spherical agglomerates crystallized in presence of inutec SP1. Turkish Journal of Pharmaceutical Sciences, 9, 101–112 (2012).

Amidon GE, Secreast PJ, Mudie D. Particle, powder, and compact characterization. In Developing Solid Oral Dosage Forms (pp. 163–186). Elsevier (2009).

Shah MK. Evaluation of physical and mechanical properties of Ibuprofen tablets using different bulking agents by means of Heckel and Kawakita Plots. Long Island University, The Brooklyn Center (2017).

Patel RD, Raval MK, Sheth NR. Formation of Diacerein–fumaric acid eutectic as a multi-component system for the functionality enhancement. Journal of Drug Delivery Science and Technology, 58, 101562 (2020).

Haware RV, Tho I, Bauer-Brandl A. Evaluation of a rapid approximation method for the elastic recovery of tablets. Powder Technology, 202(1–3), 71–77 (2010).

Garala K, Patel J, Patel A, Raval M, Dharamsi A. Influence of excipients and processing conditions on the development of agglomerates of racecadotril by crystallo-co-agglomeration. International Journal of Pharmaceutical Investigation, 2(4), 189 (2012).

Shaha D, Sorathiab K. Design and evaluation of sustained release spherical agglomerates of Fluvastatin sodium by crystallo-co-agglomeration. Journal of Applied Pharmaceutical Science, 7(9), 99–108 (2017).

Toufouki S, Ali A, Wang Y, Li R, Cao Y, Yao S. Deep eutectic solvents formed by pharmaceutical ingredients and their potential influences on solid preparations. Journal of the Serbian Chemical Society, 89(1), 107 – 121 (2023).

Chandrasekharan S, Chinnasamy G, Bhatnagar S. Sustainable phyto-fabrication of silver nanoparticles using Gmelina arborea exhibit antimicrobial and biofilm inhibition activity. Scientific Reports, 12(1), 156 (2022).

Madhvi K, Mehta K, Vadalia K, Jay C, Sandip K. Design and development of co-processed excipients for fast dissolving tablets of Irbesartan by melt agglomeration technique. Journal of Pharmaceutical Investigation, 45(2), 163–186 (2015).

Bonetto RD, Ladaga JL, Ponz E. Measuring surface topography by scanning electron microscopy. II. Analysis of three estimators of surface roughness in second dimension and third dimension. Microscopy and Microanalysis, 12(2), 178–186 (2006).

Shim H, Sah H. Assessment of residual solvent and drug in PLGA microspheres by derivative thermogravimetry. Pharmaceutics, 12(7), 626 (2020).

Kumar M, Mandal UK. In-vitro Dissolution Study of Pharmaceutical Products with USP Apparatus-IV. Drug Delivery Letters, 11(3), 195–202 (2021).

Usha AN, Mutalik S, Reddy MS, Ranjith AK, Kushtagi P, Udupa N. Preparation and, in vitro, preclinical and clinical studies of aceclofenac spherical agglomerates. European Journal of Pharmaceutics and Biopharmaceutics, 70(2), 674–683 (2008).

Klevan I, Nordström J, Tho I, Alderborn G. A statistical approach to evaluate the potential use of compression parameters for classification of pharmaceutical powder materials. European Journal of Pharmaceutics and Biopharmaceutics, 75(3), 425–435 (2010).

Maghsoodi M. Effect of process variables on physicomechanical properties of the agglomerates obtained by spherical crystallization technique. Pharmaceutical Development and Technology, 16(5), 474–482 (2011).

Parasuraman S, Sujithra J, Syamittra B, Yeng WY, Ping WY, Muralidharan S, et al. Evaluation of sub-chronic toxic effects of petroleum ether, a laboratory solvent in Sprague-Dawley rats. Journal of Basic and Clinical Pharmacy, 5(4), 89–97 (2014).

Turgeon M, Oualkacha K, Ciampi A, Miftah H, Dehghan G, Zanke BW, et al. Principal component of explained variance: an efficient and optimal data dimension reduction framework for association studies. Statistical Methods in Medical Research, 27(5), 1331–1350 (2018).

Balasubramanian P, Praharaj PT. Principal component analysis revealed the key influencing factors of kombucha bacterial cellulose yield and productivity. Bioresource Technology Reports, 23, 101539 (2023).

Ivosev G, Burton L, Bonner R. Dimensionality reduction and visualization in principal component analysis. Analytical Chemistry, 80(13), 4933–4944 (2008).

Popovicheva O, Padoan S, Schnelle-Kreis J, Nguyen D-L, Adam T, Kistler M, et al. Spring aerosol in urban atmosphere of megacity: analytical and statistical assessment for source impacts. Aerosol and Air Quality Research, 20(4), 702–717 (2020).

Patel RD, Raval MK, Bagathariya AA, Sheth NR. Functionality improvement of Nimesulide by eutectic formation with nicotinamide: Exploration using temperature-composition phase diagram. Advanced Powder Technology, 30(5), 961-73 (2019)

Patel RD, Raval MK, Pethani TM, Sheth NR. Influence of eutectic mixture as a multi-component system in the improvement of physicomechanical and pharmacokinetic properties of diacerein. Advanced Powder Technology, 31(4), 1441-56 (2020)

Raval MK, Vaghela PD, Vachhani AN, Sheth NR. Role of excipients in the crystallization of Albendazole. Advanced Powder Technology, 26(4), 1102-15 (2015).

Shelke M, Godge R, Sahane T, Pawar O, Kasar S. Stability Indicating RP-HPLC Method for Estimation of Cariprazine Hydrochloride in Human Plasma. J. Appl. Pharm. Res., 12 (2), 27-34 (2024).

Tay JYS, Liew CV, Heng PWS. Powder flow testing: judicious choice of test methods. AAPS PharmSciTech, 18, 1843-54 (2017)

Goh HP, Heng PWS, Liew CV. Comparative evaluation of powder flow parameters with reference to particle size and shape. International Journal of Pharmaceutics, 547 (1-2), 133-41 (2018)

Raval MK, Sorathiya KR, Chauhan NP, Patel JM, Parikh RK, Sheth NR. Influence of polymers/excipients on development of agglomerated crystals of secnidazole by crystallo-co-agglomeration technique to improve processability. Drug Development and Industrial Pharmacy, 39(3), 437-46 (2013)

Kawashima Y, Imai M, Takeuchi H, Yamamoto H, Kamiya K, Hino T. Improved flowability and compactibility of spherically agglomerated crystals of ascorbic acid for direct tableting designed by spherical crystallization process. Powder Technology, 130(1-3), 283-9 (2003)

Cabiscol R, Finke JH, Zetzener H, Kwade A. Characterization of mechanical property distributions on tablet surfaces. Pharmaceutics, 10(4), 184 (2018)

Kedia K, Wairkar S. Improved micromeritics, packing properties and compressibility of high dose drug, Cycloserine, by spherical crystallization. Powder Technology, 344, 665-72 (2019)

Jelić D, Papović S, Vraneš M, Gadžurić S, Berto S, Alladio E, et al. Thermo-analytical and compatibility study with mechanistic explanation of degradation kinetics of ambroxol hydrochloride tablets under non-isothermal conditions. Pharmaceutics, 13(11), 1910 (2021)

French AD, Santiago Cintrón M. Cellulose polymorphy, crystallite size, and the Segal Crystallinity Index. Cellulose, 20, 583-8 (2013)

Skotnicki M, Jadach B, Skotnicka A, Milanowski B, Tajber L, Pyda M, et al. Physicochemical characterization of a co-amorphous atorvastatin-irbesartan system with a potential application in fixed-dose combination therapy. Pharmaceutics, 13(1), 118 (2021)

Broza YY, Vishinkin R, Barash O, Nakhleh MK, Haick H. Synergy between nanomaterials and volatile organic compounds for non-invasive medical evaluation. Chemical Society Reviews, 47(13), 4781-859 (2018)

Enyoh CE, Verla AW, Qingyue W, Ohiagu FO, Chowdhury AH, Enyoh EC, et al. An overview of emerging pollutants in air: Method of analysis and potential public health concern from human environmental exposure. Trends in Environmental Analytical Chemistry, 28, e0010 (2020)