Application of dumping and transfer methods to study in vitro dissolution behavior and precipitate of the poor water soluble weak base drug: Carvedilol case

Ahmed Ali Hashim Al - Ameri; Masar Basim Mohsin Mohamed

doi:10.32947/ajps.v25i2.1163

Authors

Ahmed Ali Hashim Al - Ameri Department of Pharmaceutics, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
Masar Basim Mohsin Mohamed Department of Pharmaceutics, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq

DOI:

https://doi.org/10.32947/ajps.v25i2.1163

Keywords:

Carvedilol, transfer method, dumping method, poor water soluble weak base drug, precipitate

Abstract

This work intended to evaluate the dissolution of poor water soluble weakly basic drug like carvedilol (Carv) via two methods used to study and assess the effect of pH changes from the stomach to the small intestine on the drug dissolution and precipitation (ppt): dumping and transfer. Three approaches were used to increase solubility and decrease the precipitation of carvedilol; first, the acid modification principle was by incorporating Carv with fumaric acids (FA) to keep the drug at a low pH in the intestine. The second approach was solvent evaporation, which converted the drug from a low soluble crystalline form to a highly soluble amorphous form, and the last approach was forming a slow-release floating dosage form. The prepared samples were investigated by FESEM and FTIR. There is a slight shift in the peaks related to the hydroxyl group in approaches (acid modification and solvent evaporation) compared to the peak’s position in the Carv spectrograms, and the FESEM shows a decrease in particle sizes of prepared samples. The Carv prepared samples in vitro dissolution of dumping, and the transfer showed different in vitro dissolution profiles with enhanced dissolution profiles and lower ppt amount. The amorphization technique’s ppt was highly decreased in both dissolution dumping and transfer methods compared to the in vitro dissolution of the control of Carv.

References

1- Hamed R, Awadallah A, Sunoqrot S, Tarawneh O, Nazzal S, AlBaraghthi T, et al. pH-dependent solubility and dissolution behavior of carvedilol—case example of a weakly basic BCS class II drug. Aaps Pharmscitech. 2016;17:418-26.

2- Mehsen MB. Effect of propylene glycol, poly ethylene glycol 400 and pH on the release and diffusion of Ibuprofen from different topical bases. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2011;9(1):80-93.

3- Li S, Pollock-Dove C, Dong LC, Chen J, Creasey AA, Dai W-G. Enhanced bioavailability of a poorly water-soluble weakly basic compound using a combination approach of solubilization agents and precipitation inhibitors: a case study. Molecular pharmaceutics. 2012;9(5):1100-8.

4- Alqahtani MS, Kazi M, Alsenaidy MA, Ahmad MZ. Advances in oral drug delivery. Frontiers in pharmacology. 2021;12:618411.

5- Naqvi A, Ahmad M, Minhas MU, Khan KU, Batool F, Rizwan A. Preparation and evaluation of pharmaceutical co-crystals for solubility enhancement of atorvastatin calcium. Polymer Bulletin. 2020;77:6191-211.

6- Dulin B, Abraham WT. Pharmacology of carvedilol. The American journal of cardiology. 2004;93(9):3-6.

7- Kim D, Kim Y, Tin Y-Y, Soe M-T-P, Ko B, Park S, et al. Recent technologies for amorphization of poorly water-soluble drugs. Pharmaceutics. 2021;13(8):1318.

8- Neetika B, Manish G. Floating drug delivery system. IJPRAS. 2012;1(4):20-8.

9- Ruff A, Fiolka T, Kostewicz ES. Prediction of Ketoconazole absorption using an updated in vitro transfer model coupled to physiologically based pharmacokinetic modelling. European Journal of Pharmaceutical Sciences. 2017;100:42-55.

10- Abdelwahab NS. Spectrophotometric methods for simultaneous determination of Carvedilol and Hydrochlorothiazide in combined dosage form. Arabian Journal of Chemistry. 2016;9:S355-S60.

11- Sharapova AV, Ol'khovich MV, Blokhina SV. Thermodynamic consideration of dissolution and distribution behavior of carvedilol in pharmaceutical significant media. The Journal of Chemical Thermodynamics. 2024;190:107207.

12- Van Eerdenbrugh B, Baird JA, Taylor LS. Crystallization tendency of active pharmaceutical ingredients following rapid solvent evaporation—classification and comparison with crystallization tendency from under cooled melts. Journal of pharmaceutical sciences. 2010;99(9):3826-38.

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

14- SABAR MH, JAAFAR IS, MOHAMED MBM. IN SITU GEL AS PLATFORM FOR KETOCONAZOLE SLOW RELEASE DOSAGE FORM. Int J App Pharm. 2018;10(5):76-80.

15- Griffiths PR. Fourier transform infrared spectrometry. Science. 1983;222(4621):297-302.

16- Deng H, Hu X, Li HA, Luo B, Wang W. Improved pore-structure characterization in shale formations with FESEM technique. Journal of Natural Gas Science and Engineering. 2016;35:309-19.

17- Hamed R, Kamal A. Concentration profiles of carvedilol: a comparison between in vitro transfer model and dissolution testing. Journal of Pharmaceutical Innovation. 2019;14:123-31.

18- Carlert S, Pålsson A, Hanisch G, Von Corswant C, Nilsson C, Lindfors L, et al. Predicting intestinal precipitation—a case example for a basic BCS class II drug. Pharmaceutical research. 2010;27:2119-30.

19- Cristofoletti R, Dressman JB. Dissolution methods to increasing discriminatory power of in vitro dissolution testing for ibuprofen free acid and its salts. Journal of pharmaceutical sciences. 2017;106(1):92-9.

20- Patel S, Zhu W, Xia B, Sharma N, Hermans A, Ehrick JD, et al. Integration of precipitation kinetics from an in vitro, multicompartment transfer system and mechanistic oral absorption modeling for pharmacokinetic prediction of weakly basic drugs. Journal of pharmaceutical sciences. 2019;108(1):574-83.

21- Parikh RK, Parikh DC, Delvadia RR, Patel SM. A novel multicompartment dissolution apparatus for evaluation of floating dosage form containing poorly soluble weakly basic drug. Dissolution Technologies. 2006;13(1):14.

22- Thenge R, Patel R, Kayande N, Mahajan N. Co-crystals of carvedilol: preparation, characterization and evaluation. Int J Appl Pharm. 2020;12(1):42-9.

23- KADDOORI ZS, MOHAMED MBM, NUMAN NA, AL-FALAHI NHR. Application of stearic acid in organogel as a floating system. International Journal of Pharmaceutical Research (09752366). 2020.

24- Mohamed MBM, Qaddoori ZS, Hameed GS. Study the Effect of 12-Hydroxyoctadecanoic Acid Concentration on Preparation and Characterization of Floating Organogels using Cinnarizin as Modeling Drug. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2022;31(2):169-76.

25- Mohamed M. Oily in situ gels as an alternative floating platform for ketoconazole release. International Journal of Research in Pharmaceutical Sciences. 2020;11(2):2638-49.

26- Streubel A, Siepmann J, Dashevsky A, Bodmeier R. pH-independent release of a weakly basic drug from water-insoluble and-soluble matrix tablets. Journal of controlled release. 2000;67(1):101-10.

27- Li S, Pollock-Dove C, Dong LC, Chen J, Creasey AA, Dai W-G. Enhanced bioavailability of a poorly water-soluble weakly basic compound using a combination approach of solubilization agents and precipitation inhibitors: a case study. Molecular pharmaceutics2012. p. 1100-8.

28- Lim D-K, Bae J-W, Song B-J, Jo H-S, Kim H-E, Lee D-W, et al. Effect of Manufacturing Method and Acidifier on the Dissolution Rate of Carvedilol from Solid Dispersion Formulations. Journal of pharmaceutical investigation. 2011;41(6):363-9.

29- Khalil MR, Hameed GS, Hanna DB. Preparation and Evaluation of Azithromycin as Rectal Suppository to Treat Bacterial Infection of COVID-19. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512). 2023;32(3):60-70.

30- Hameed GS. Controlling phase transformation during milling in the pre-formulation of Active pharmaceutical Ingredients. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2019;19(2):37-46.