DOI: https://doi.org/10.24959/nphj.19.14

Approaches of increasing oral bioavailability of class ii active pharmaceutical ingredients in accordance with the biopharmaceutical classification system

V. V. Mohylyuk, L. L. Davtian, D. O. Novykov, M. G. Katynska, Yu. V. Shmyrova, O. O. Dobrovolnyi

Abstract


Aim. To compare existing approaches used for enhancing oral bioavailability (BA) of class II active pharmaceutical ingredients (API) and categorize them in the order of most promising.
Materials and methods. The material of the article was literary data about approaches used for enhancing oral bioavailability of class II active pharmaceutical ingredients with a high permeability and poor solubility. Methods of information search, methods of comparison and generalization, systematic methods were used to carry out the research
tasks.
Results and discussion. During last 20 years, the share of class II API in accordance with the biopharmaceutical classification system (i.e. with low solubility and high permeability) is continuously increasing at the world market and different stages of pharmaceutical product development. The approaches to improving oral BA of class II API which can be used to develop generic and modified generic drugs have been discussed in this article. These approaches were considered from the point of view of the principle of increasing the oral BA. It is concluded that promising approaches to increase oral BA should meet the following requirements: rapid achievement of oversaturated API concentration and its subsequent maintenance, keeping the whole API dose dissolved during transit through the intestines. Increased solubility and specific surface area are used as the main levers in all these approaches to improve oral bioavailability. At the same time, the ability to form supersaturated solutions and the retention of high concentrations during transit through the intestine differs depending on the approach.

Conclusions. The most promising approaches to increase oral bioavailability, contributing to the formation of supersaturated solutions and maintaining high concentrations during transit are included: solid amorphous dispersions of API; digestible formulations that form micelles/emulsions in the intestine; and digestible inclusion complexes with cyclodextrins.


Keywords


biopharmaceutical classification system; oral bioavailability; pH-dependent solubility; supersaturated solution; dissolution kinetics; solid amorphous dispersion; lipid formulations; cyclodextrins

References


Amidon, G. L., Lennernäs, H., Shah, V. P., Crison, J. R. (1995). A theoretical basis for a biopharmaceutic drug classification : the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical research, 12 (3), 413–420.

Oh, D. M., Curl, R. L., Amidon, G. L. (1993). Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans : a mathematical model. Pharmaceutical research, 10 (2), 264–270.

Ting, J. M., Porter, W. W., Mecca, J. M., Bates, F. S., & Reineke, T. M. (2018). Advances in Polymer Design for Enhancing Oral Drug Solubility and Delivery. Bioconjugate Chemistry, 29 (4), 939–952. https://doi.org/10.1021/acs.bioconjchem.7b00646

Liu, R. (2008). Water–insoluble drug formulation (Second Edition). Boca Raton: CRC Press, 685 p.

Singh, A., Worku, Z. A., Van den Mooter, Z. A. (2011). Oral formulation strategies to improve solubility of poorly water-soluble drugs. Expert opinion on drug delivery, 8 (10), 1361–1378. https://doi.org/10.1517/17425247.2011.606808

McConnell, E. L., Fadda, H. M., Basit, A. W. (2008). Gut instincts : explorations in intestinal physiology and drug delivery. International

journal of pharmaceutics, 364 (2), 213–226. https://doi.org/10.1016/j.ijpharm.2008.05.012

Potthast, H., Dressman, J. B., Junginger, H. E., Midha, K. K., Oeser, H., Shah, V. P., Barends, D. M. (2005). Biowaiver monographs for immediate release solid oral dosage forms : Ibuprofen. Journal of pharmaceutical sciences, 94 (10), 2121–2131.

Vogelpoel, H., Welink, J., Amidon, G. L., Junginger, H. E., Midha, K. K., Möller, H., … Barends, D. M. (2004). Biowaiver monographs for immediate release solid oral dosage forms based on biopharmaceutics classification system (BCS) literature data : Verapamil hydrochloride, propranolol hydrochloride, and atenolol. Journal of Pharmaceutical Sciences, 93 (8), 1945–1956. https://doi.org/10.1002/jps.20131

Bavishi, D. D., & Borkhataria, C. H. (2016). Spring and parachute : How cocrystals enhance solubility. Progress in Crystal Growth and Characterization of Materials, 62 (3), 1–8. https://doi.org/10.1016/j.pcrysgrow.2016.07.001

Kuentz, M. (2018). Drug supersaturation during formulation digestion, including real–time analytical approaches. Advanced drug delivery reviews. Available at : https://www.researchgate.net/publication/328919123_Drug_supersaturation_during_formulation_digestion_including_real-time_analytical_approaches

Curry, S. H., Whelpton, R. (2017). Introduction to Drug Disposition and Pharmacokinetics. John Wiley & Sons, 336.

Jermain, S. V., Brough, C., & Williams, R. O. (2018). Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery – An update. International Journal of Pharmaceutics, 535 (1-2), 379–392. https://doi.org/10.1016/j.ijpharm.2017.10.051

Davis, M., & Walker, G. (2018). Recent strategies in spray drying for the enhanced bioavailability of poorly water–soluble drugs. Journal of Controlled Release, 269, 110–127. https://doi.org/10.1016/j.jconrel.2017.11.005

Chaudhari, S., & Gupte, A. (2017). Mesoporous Silica as a Carrier for Amorphous Solid Dispersion. British Journal of Pharmaceutical Research, 16 (6), 1–19. https://doi.org/10.9734/bjpr/2017/33553

Démuth, B., Nagy, Z. K., Balogh, A., Vigh, T., Marosi, G., Verreck, G., … Brewster, M. E. (2015). Downstream processing of polymer-based amorphous solid dispersions to generate tablet formulations. International Journal of Pharmaceutics, 486 (1–2), 268–286. https://doi.org/10.1016/j.ijpharm.2015.03.053

Kalepu, S., & Nekkanti, V. (2015). Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharmaceutica

Sinica B, 5 (5), 442–453. https://doi.org/10.1016/j.apsb.2015.07.003

Pouton, C. W. (2006). Formulation of poorly water–soluble drugs for oral administration : Physicochemical and physiological issues and the lipid formulation classification system. European Journal of Pharmaceutical Sciences, 29 (3-4), 278–287. https://doi.org/10.1016/j.ejps.2006.04.016

Jannin, V. (2018). Complex Interplay Between Solubilization, Digestion, Supersaturation and Absorption of Poorly Soluble Drugs with Lipid–Based Formulations. Current Drug Delivery, 15 (6), 749–751. https://doi.org/10.2174/1567201814666171018120817

Di Cagno, M., Terndrup Nielsen, T., Lambertsen Larsen, K., Kuntsche, J., & Bauer–Brandl, A. (2014). β–Cyclodextrin-dextran polymers for the solubilization of poorly soluble drugs. International Journal of Pharmaceutics, 468 (1-2), 258–263. https://doi.org/10.1016/j.ijpharm.2014.04.029

Lumholdt, L. R., Holm, R., Jørgensen, E. B., & Larsen, K. L. (2012). In vitro investigations of α-amylase mediated hydrolysis of cyclodextrins in the presence of ibuprofen, flurbiprofen, or benzo[a]pyrene. Carbohydrate Research, 362, 56–61.

https://doi.org/10.1016/j.carres.2012.09.018


GOST Style Citations


1. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability / G. L. Amidon, H. Lennernäs, V. P. Shah, J. R. Crison // Pharmac. Res. – 1995. – № 12 (3). – Р. 413–420.

 

2. Oh, D. M. Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: a mathematical model / D. M. Oh, R. L. Curl, G. L.Amidon // Pharmac. Res. – 19 93. – № 10 (2). – Р. 264–270.


3. Advances in polymer design for enhancing oral drug solubility and delivery / J. M. Ting, W. W. Porter, J. M. Mecca et al. // Bioconjugate
Chem. – 2018. – № 29 (4). – Р. 939–952. https://doi.org/10.1021/acs.bioconjchem.7b00646


4. Liu, R. Water–insoluble drug formulation / R. Liu. – Second Edition. – Boca Raton : CRC Press, 2008. – 685 p.


5. Singh, A. Oral formulation strategies to improve solubility of poorly water–soluble drugs / A.Singh, Z. A.Worku, G.Van den Mooter // Expert Opinion on Drug Delivery. – 2011. – № 8 (10). – Р. 1361–1378. https://doi.org/10.1517/17425247.2011.606808


6. McConnell, E. L.Gut instincts : explorations in intestinal physiology and drug delivery / E. L.McConnell, H. M. Fadda, A. W. Basit // Intern. J. of Pharmac. – 2008. – № 364 (2). – Р. 213–226. https://doi.org/10.1016/j.ijpharm.2008.05.012


7. Biowaiver monographs for immediate release solid oral dosage forms : Ibuprofen / H. Potthast, J. B. Dressman, H. E. Junginger et al. // J. of Pharmac. Sci. – 2005. – № 94 (10). – Р. 2121–2131.


8. Biowaiver monographs for immediate release solid oral dosage forms based on biopharmaceutics classification system (BCS) literature data : Verapamil hydrochloride, propranolol hydrochloride, and atenolol / H. Vogelpoel, J. Welink, G. L. Amidon et al. // J. of Pharmac. Sci. – 2004. – № 93 (8). – Р. 1945–1956. https://doi.org/10.1002/jps.20131


9. Bavishi, D. D. Spring and parachute : how cocrystals enhance solubility / D. D. Bavishi, C. H. Borkhataria // Progress in Crystal Growth and Characterization of Materials. – 2016. – № 62 (3). – Р. 1–8. https://doi.org/10.1016/j.pcrysgrow.2016.07.001


10. Kuentz, M. Drug supersaturation during formulation digestion, including real-time analytical approaches / M. Kuentz // Advanced Drug Delivery Rev. – 2018. – [Електронний ресурс]. – Available at : https://www.researchgate.net/publication/328919123_Drug_supersaturation_during_formulation_digestion_including_real-time_analytical_approaches


11. Curry, S. H. Introduction to Drug Disposition and Pharmacokinetics / S. H. Curry, R. Whelpton. – John Wiley & Sons, 2017. – 336 р.


12. Jermain, S. V. Amorphous solid dispersions and nanocrystal technologies for poorly water–soluble drug delivery–An update / S. V. Jermain, C. Brough, R. O. Williams III // Intern. J. of Pharmac. – 2018. – № 535 (1-2). – Р. 379–392. https://doi.org/10.1016/j.ijpharm.2017.10.051


13. Davis, M. Recent strategies in spray drying for the enhanced bioavailability of poorly water–soluble drugs / M. Davis, G. Walker // J. of Controlled Release. – 2018. – № 269. – Р. 110–127. https://doi.org/10.1016/j.jconrel.2017.11.005


14. Chaudhari, S. P. Mesoporous Silica as a Carrier for Amorphous Solid Dispersion / S. P. Chaudhari, A. Gupte // British J. of Pharmac. Res. – 2017. – № 16 (6). – Р. 1–19. https://doi.org/10.9734/bjpr/2017/33553

15. Downstream processing of polymer–based amorphous solid dispersions to generate tablet formulations / B. Démuth, Z. K. Nagy, A. Balogh et al. // Intern. J. of Pharmac. – 2015. – № 486 (1–2 ). – Р. 268–286. https://doi.org/10.1016/j.ijpharm.2015.03.053


16. Kalepu, S. Insoluble drug delivery strategies: review of recent advances and business prospects / S. Kalepu, V. Nekkanti // Acta PharmaceuticaSinica B. – 2015. – Vol. 5 (5). – P. 442–453. https://doi.org/10.1016/j.apsb.2015.07.003


17. Pouton, C. W. Formulation of poorly water–soluble drugs for oral administration : physicochemical and physiological issues and the lipid formulation classification system / C. W. Pouton // Eur. J. of Pharmac. Sci. – 2006. – Vol. 29 (3–4). – P. 278–287. https://doi.org/10.1016/j.ejps.2006.04.016

 

18. Jannin, V. Complex Interplay Between Solubilization, Digestion, Supersaturation and Absorption of Poorly Soluble Drugs with Lipid–Based Formulations / V. Jannin // Current Drug Delivery. – 2018. – Vol. 15 (6). – P. 749–751. https://doi.org/10.2174/1567201814666171018120817


19. β–Cyclodextrin-dextran polymers for the solubilization of poorly soluble drugs / M. Di Cagno, T. T. Nielsen, K. L. Larsen et al. // Intern. J. of Pharmac. – 2014. – Vol. 468 (1-2). – P. 258–263. https://doi.org/10.1016/j.ijpharm.2014.04.029


20. In vitro investigations of α–amylase mediated hydrolysis of cyclodextrins in the presence of ibuprofen, flurbiprofen, or benzo [a] pyrene / L. R. Lumholdt, R. Holm, E. B. Jørgensen, K. L. Larsen // Carbohydrate Res. – 2012. – Vol. 362. – P. 56–61. https://doi.org/10.1016/j.carres.2012.09.018





Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abbreviated key title: Vìsn. farm.

ISSN 2415-8844 (Online), ISSN 1562-7241 (Print)