Preparation and Characterization of Carvedilol Solid Dispersion by Kneading Method

Ali Q. Hatem; Wedad K. Ali

doi:10.32947/ajps.v23i4.1092

Authors

Ali Q. Hatem Department of Biopharmaceutics, Collage of Pharmacy, Mustansiriyah University, Iraq
Wedad K. Ali Department of Biopharmaceutics, Collage of Pharmacy, Mustansiriyah University, Iraq

DOI:

https://doi.org/10.32947/ajps.v23i4.1092

Keywords:

Solid dispersion · Carvedilol (CVD) ·Hydrophilic carrier · Solubility · Bioavailability

Abstract

Solid dispersion using hydrophilic carrier is one of the approaches that has a potential to increase solubility, dissolution rate and consequently the oral bioavailability of poorly-water soluble drugs. In this study, class II drug "Carvedilol" (CVD) was used because of its poor solubility, it serves as a model drug that contributes to irregular dissolution and limited bioavailability. CVD: PVP K30 solid dispersion formulations SD1, SD2 and SD3 were prepared by kneading method at different weight ratios ,1:1; 1:2 and 1:4 respectively and evaluated for drug content, solubility and dissolution rate. Kneading method enhances the stability of drugs and suitable for processing thermolabile substances. The optimum solid dispersion ratio was characterized also for drug-carrier interaction by FTIR spectroscopy, and crystallinity by SEM and PXRD and compared with physical mixture and pure drug powder.

The results showed that the solubility of carvedilol increased by increasing the proportion of PVP K30 used in the dispersion of the drug. On the other hand, dissolution study revealed a significant enhancement in the dissolution rate of the drug using solid dispersion compared to pure drug and physical mixture. X-ray diffraction of the solid dispersion suggest that the drug's transformation from crystalline to amorphous form may be responsible for the observed improvement in dissolving rate. The carvedilol solid dispersion improved the solubility and dissolution, which depend on the carrier concentration ratio. The dissolution of drugs increased with an increase in carrier content. The studies of PXRD, SEM, and FTIR revealed the amorphous nature of the drug in solid dispersion. The solid dispersion by kneading approach using PVP K30 as a carrier is a potential method for improving CVD's solubility and dissolution rate.

References

- PB C, Kolhe M, Dhamak K, Bhor R. Analytical Technique for Carvedilol and Ivabradine Determination from Pure and Pharmaceutical Dosage Forms: A Review.

- Pfleger J, Gresham K, Koch WJ. G protein-coupled receptor kinases as therapeutic targets in the heart. Nature Reviews Cardiology. 2019;16(10):612-22. DOI: https://doi.org/10.1038/s41569-019-0220-3

- Alves JMV, Prado LD, Rocha HVA. Evaluation and correlation of the physicochemical properties of carvedilol. Pharmaceutical development and technology. 2016;21(7):856-66. DOI: https://doi.org/10.3109/10837450.2015.1073740

- Prado LD, Rocha HVA, Resende JALC, Ferreira GB, de Figuereido Teixeira AMR. An insight into carvedilol solid forms: effect of supramolecular interactions on the dissolution profiles. CrystEngComm. 2014;16(15):3168-79. DOI: https://doi.org/10.1039/C3CE42403K

- Brittain HG. Polymorphism in pharmaceutical solids. Drugs and the pharmaceutical sciences. 1999;95:183-226.

- Desiraju GR. Polymorphism: the same and not quite the same. Crystal Growth and Design. 2008;8(1):3-5. DOI: https://doi.org/10.1021/cg701000q

- Praveen R, Verma PRP, Venkatesan J, Yoon D-H, Kim S-K, Singh SK. In vitro and in vivo evaluation of gastro-retentive carvedilol loaded chitosan beads using Gastroplus™. International Journal of Biological Macromolecules. 2017;102:642-50. DOI: https://doi.org/10.1016/j.ijbiomac.2017.04.067

- Salehi N, Kuminek G, Al-Gousous J, Sperry DC, Greenwood DE, Waltz NM, et al. Improving dissolution behavior and oral absorption of drugs with pH-dependent solubility using ph modifiers: a physiologically realistic mass transport analysis. Molecular Pharmaceutics. 2021;18(9):3326-41. DOI: https://doi.org/10.1021/acs.molpharmaceut.1c00262

- Tsume Y, Mudie DM, Langguth P, Amidon GE, Amidon GL. The Biopharmaceutics Classification System: subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC. European Journal of Pharmaceutical Sciences. 2014;57:152-63. DOI: https://doi.org/10.1016/j.ejps.2014.01.009

- Repka MA, Bandari S, Kallakunta VR, Vo AQ, McFall H, Pimparade MB, et al. Melt extrusion with poorly soluble drugs–An integrated review. International journal of pharmaceutics. 2018;535(1-2):68-85. DOI: https://doi.org/10.1016/j.ijpharm.2017.10.056

- Vyas J, Daxini K, Vyas P. Formulation of PEG-based Solid Dispersion for Dissolution rate Enhancement of Modafinil. Research Journal of Pharmaceutical Dosage Forms and Technology. 2020;12(1):1-6. DOI: https://doi.org/10.5958/0975-4377.2020.00001.4

- Gupta J, Gupta R. Effect of Hydrophilic Carriers for Solubility and Dissolution Enhancement of Sulfamerazine by Solid Dispersions Technique. 2021. DOI: https://doi.org/10.9734/jpri/2021/v33i54A33752

- Norouzi F, Jouyban A, Martinez F, Barzegar-Jalali M, Rahimpour E. Solubility of celecoxib in carbitol+ water mixtures at various temperatures: experimental data and mathematical modelling. Physics and Chemistry of Liquids. 2019;57(6):755-67. DOI: https://doi.org/10.1080/00319104.2018.1519712

- Mukesh S, Joshi P, Bansal AK, Kashyap MC, Mandal SK, Sathe V, et al. Amorphous Salts Solid Dispersions of Celecoxib: Enhanced Biopharmaceutical Performance and Physical Stability. Molecular Pharmaceutics. 2021;18(6):2334-48. DOI: https://doi.org/10.1021/acs.molpharmaceut.1c00144

- Volkova TV, Domanina EN, Chislov MV, Proshin AN, Terekhova IV. Polymeric composites of 1, 2, 4-thiadiazole: solubility, dissolution and permeability assay. Journal of Thermal Analysis and Calorimetry. 2020;140(5):2305-15. DOI: https://doi.org/10.1007/s10973-019-08947-6

- Rehman A, Iqbal M, Khan BA, Khan MK, Huwaimel B, Alshehri S, et al. Fabrication, in vitro, and in vivo assessment of eucalyptol-loaded nanoemulgel as a novel paradigm for wound healing. Pharmaceutics. 2022;14(9):1971. DOI: https://doi.org/10.3390/pharmaceutics14091971

- Ibrahim TM, Abdallah MH, El-Megrab NA, El-Nahas HM. Transdermal ethosomal gel nanocarriers; a promising strategy for enhancement of anti-hypertensive effect of carvedilol. Journal of liposome research. 2019;29(3):215-28. DOI: https://doi.org/10.1080/08982104.2018.1529793

- Colombo M, Minussi C, Orthmann S, Staufenbiel S, Bodmeier R. Preparation of amorphous indomethacin nanoparticles by aqueous wet bead milling and in situ measurement of their increased saturation solubility. European Journal of Pharmaceutics and Biopharmaceutics. 2018;125:159-68. DOI: https://doi.org/10.1016/j.ejpb.2018.01.013

- Csicsák D, Borbás E, Kádár S, Tőzsér P, Bagi P, Pataki H, et al. Towards more accurate solubility measurements with real time monitoring: A carvedilol case study. New Journal of Chemistry. 2021;45(26):11618-25. DOI: https://doi.org/10.1039/D1NJ01349A

- Ahsan W, Alam S, Javed S, Alhazmi HA, Albratty M, Najmi A, et al. Study of Drug Release Kinetics of Rosuvastatin Calcium Immediate-Release Tablets Marketed in Saudi Arabia. Dissolution Technol. 2022;29. DOI: https://doi.org/10.14227/DT290222PGC1

- Tapas A, Kawtikwar P, Sakarkar D. An improvement in physicochemical properties of carvedilol through spherically agglomerated solid dispersions with PVP K30. Acta Poloniae Pharmaceutica-Drug Research. 2012;69(2):299-308.

- Gupta V, Ain S, Babita K, Ain Q, Dahiya J. Solubility enhancement of the poorly water-soluble antiulcer drug famotidine by inclusion complexation. IJPSN. 2013;6(1):1983-9. DOI: https://doi.org/10.37285/ijpsn.2013.6.1.10

- Stevie FA, Garcia R, Shallenberger J, Newman JG, Donley CL. Sample handling, preparation and mounting for XPS and other surface analytical techniques. Journal of Vacuum Science & Technology A: Vacuum, Surfaces, and Films. 2020;38(6):063202. DOI: https://doi.org/10.1116/6.0000421

- Ali HSM, Khan SA. Stabilization of various zero-valent metal nanoparticles on a superabsorbent polymer for the removal of dyes, nitrophenol, and pathogenic bacteria. ACS omega. 2020;5(13):7379-91. DOI: https://doi.org/10.1021/acsomega.9b04410

- Incecayir T. The effects of surfactants on the solubility and dissolution profiles of a poorly water-soluble basic drug, carvedilol. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 2015;70(12):784-90.

- Kaewnopparat N, Kaewnopparat S, Jangwang A, Maneenaun D, Chuchome T, Panichayupakaranant P. Increased solubility, dissolution and physicochemical studies of curcumin-polyvinylpyrrolidone K-30 solid dispersions. World Academy of Science, Engineering and Technology. 2009;55:229-34.

- Yurtdaş-Kırımlıoğlu G. Development and characterization of lyophilized cefpodoxime proxetil-Pluronic® F127/polyvinylpyrrolidone K30 solid dispersions with improved dissolution and enhanced antibacterial activity. Pharmaceutical Development and Technology. 2021;26(4):476-89. DOI: https://doi.org/10.1080/10837450.2021.1889584

- Ravikumar AA, Kulkarni PK, Osmani RAM, Hani U, Ghazwani M, Fatease AA, et al. Carvedilol Precipitation Inhibition by the Incorporation of Polymeric Precipitation Inhibitors Using a Stable Amorphous Solid Dispersion Approach: Formulation, Characterization, and In Vitro In Vivo Evaluation. Polymers. 2022;14(22):4977. DOI: https://doi.org/10.3390/polym14224977

- Sharma A, Jain C. Preparation and characterization of solid dispersions of carvedilol with PVP K30. Research in pharmaceutical sciences. 2010;5(1):49.

- Lewis S, Lewis A, Lewis P. Prediction of glycoprotein secondary structure using ATR-FTIR. Vibrational Spectroscopy. 2013;69:21-9. DOI: https://doi.org/10.1016/j.vibspec.2013.09.001

- Bahmani K, Singla Y. ENHANCED SOLUBILITY OF ANTIHYPERTENSIVE DRUG USING HYDROPHILIC CARRIER BASED POTENT SOLID DISPERSION SYSTEMS. studies. 2018;3:110.

- Krstić M, Manić L, Martić N, Vasiljević D, Mračević SĐ, Vukmirović S, et al. Binary polymeric amorphous carvedilol solid dispersions: In vitro and in vivo characterization. European Journal of Pharmaceutical Sciences. 2020;150:105343. DOI: https://doi.org/10.1016/j.ejps.2020.105343

- Kajdič S, Vrečer F, Kocbek P. Preparation of poloxamer-based nanofibers for enhanced dissolution of carvedilol. European Journal of Pharmaceutical Sciences. 2018;117:331-40. DOI: https://doi.org/10.1016/j.ejps.2018.03.006

- Badshah SF, Akhtar N, Minhas MU, Khan KU, Khan S, Abdullah O, et al. Porous and highly responsive cross-linked β-cyclodextrin based nanomatrices for improvement in drug dissolution and absorption. Life Sciences. 2021;267:118931. DOI: https://doi.org/10.1016/j.lfs.2020.118931