EFFECTS OF DRYING TEMPERATURE ON CURCUMIN AND PIPERINE DISSOLUTION AND THE RELEASE KINETICS OF SOLID DISPERSION-BASED MICROPARTICLES: A PRELIMINARY STUDY
Yıl 2023,
, 853 - 863, 20.09.2023
Monica Octaviani Tiara Dewi
,
Dewi Setyaningsih
Öz
Objective: One of the major challenges in developing curcumin as a pharmaceutical agent is its low bioavailability after oral administration. Co-administration of curcumin-piperine combined with employing solid dispersions (SD) approach has been shown to enhance curcumin dissolution and bioavailability. Understanding the influence of the processing temperature during spray drying is crucial in SDs preparations; the purpose of this study is to inquire the effect of inlet temperature spray-dryer on dissolution behavior and the best-fit kinetic model of dissolution itself.
Material and Method: The SD powder was prepared using a spray-drying method by varying the inlet temperature (105°C; 115°C; 125°C) and involved polyvinyl alcohol (PVA) as a carrier. The SD were prepared at 30% Curcuma longa and 10% Piper nigrum extracts. Yield (%) of the dried powder resulted from the spray drying process was monitored, and dissolution behavior of curcumin and piperine were analyzed using a dissolution efficiency (DE) value. Furthermore, mathematical model describing the release mechanism of curcumin and piperine from the dissolution were evaluated using a DDSolver software.
Result and Discussion: The variation of drying temperature on the spray dryer affects the dissolution behavior and the % yield of the PVA-based SD containing C. longa and P. nigrum extract. The most ideal mathematical model of kinetic release for curcumin and piperine were the Quadratic model, indicating that the mechanism of dissolution is diffusion through a gap between the PVA particle and the surrounding medium.
Destekleyen Kurum
Sanata Dharma University
Proje Numarası
007 Penel./LPPM-USD/II/2022
Teşekkür
Sanata Dharma University of Center for Research and Community Services
Kaynakça
- 1. Ashraf, K., Mujeeb, M., Ahmad, A., Ahmad, N., Amir, M. (2015). Determination of curcuminoids in Curcuma longa Linn. by UPLC/Q-TOF-MS: An application in turmeric cultivation. Journal of Chromatographic Science, 53(8), 1346-1352. [CrossRef]
- 2. Wan, S., Sun, Y., Qi, X., Tan, F. (2012). Improved bioavailability of poorly water-soluble drug curcumin in cellulose acetate solid dispersion. AAPS PharmSciTech, 13(1), 159-166. [CrossRef]
- 3. Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran, R., Srinivas, P.S.S.R. (1998). Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica, 64(4), 353-356. [CrossRef]
- 4. Gorgani, L., Mohammadi, M., Najafpour, G.D., Nikzad, M. (2017). Piperine-The bioactive compound of black pepper: From isolation to medicinal formulations. Comprehensive Reviews in Food Science and Food Safety, 16(1), 124-140. [CrossRef]
- 5. Chopra, B., Dhingra, A.K., Kapoor, R.P., Prasad, D.N. (2017). Piperine and its various physicochemical and biological aspects: A review. Open Chemistry Journal, 3(1), 75-96. [CrossRef]
- 6. Sachin, S., Nirmala, G., Subir, B., Suresh, J., Dushyant, G. (2012). Development and validation of UV spectroscopic method for the quick estimation of gingerol from Zingiber officinale rhizome extract. International Research Journal of Pharmacy, 3(5), 234-237.
- 7. Patil, V., Chauhan, A.K., Singh, R.P. (2014). Optimization of the spray-drying process for developing guava powder using response surface methodology. Powder Technology, 253, 230-236. [CrossRef]
- 8. Cano-Chauca, M., Stringheta, P.C., Ramos, A.M., Cal-Vidal, J. (2005). Effect of the carriers on the microstructure of mango powder obtained by spray drying and its functional characterization. Innovative Food Science and Emerging Technologies, 6(4), 420-428. [CrossRef]
- 9. Lee, K.C., Yoon, Y.S., Li, F.Z., Eun, J.B. (2017). Effects of inlet air temperature and concentration of carrier agents on physicochemical properties, sensory evaluation of spray-dried mandarin (Citrus unshiu) beverage powder. Applied Biological Chemistry, 60(1), 33-40. [CrossRef]
- 10. Shi, Y., Wang, J., Wang, Y., Zhang, H., Ma, Y., Zhao, X., Zhang, C. (2018). Inlet temperature affects spray drying quality of watermelon powder. Czech Journal of Food Sciences, 36(4), 316-323. [CrossRef]
- 11. Santhalakshmy, S., Don Bosco, S.J., Francis, S., Sabeena, M. (2015). Effect of inlet temperature on physicochemical properties of spray-dried jamun fruit juice powder. Powder Technology, 274, 37-43. [CrossRef]
- 12. Teera-Arunsiri, A., Suphantharika, M., Ketunuti, U. (2009). Preparation of spray-dried wettable powder formulations of Bacillus thuringiensis-based biopesticides. Journal of Economic Entomology, 96(2), 292-299. [CrossRef]
- 13. Hu, L., Shi, Y., Li, J.H., Gao, N., Ji, J., Niu, F., Chen, Q., Yang, X., Wang, S. (2015). Enhancement of oral bioavailability of curcumin by a novel solid dispersion system. AAPS PharmSciTech, 16(6), 1327-1334. [CrossRef]
- 14. Wang, R., Han, J., Jiang, A., Huang, R., Fu, T., Wang, L., Zheng, Q., Li, W., Li, J. (2019). Involvement of metabolism-permeability in enhancing the oral bioavailability of curcumin in excipient-free solid dispersions co-formed with piperine. International Journal of Pharmaceutics, 561, 9-18. [CrossRef]
- 15. Jumah, R.Y., Tashtoush, B., Shaker, R.R., Zraiy, A.F. (2000). Manufacturing parameters and quality characteristics of spray dried jameed. Drying Technology, 18(4-5), 967-984. [CrossRef]
- 16. Muzaffar, K., Kumar, P. (2017). Spray drying of tamarind pulp: Effect of process parameters using protein as carrier agent. Journal of Food Processing and Preservation, 41(2), e12781. [Crossref]
- 17. Fujita, A., Souza, V.B., Daza, L.D., Fávaro-Trindade, C.S., Granato, D., Genovese, M.I. (2017). Effects of spray-drying parameters on in vitro functional properties of camu-camu (Myrciaria dubia Mc. Vaugh): A typical Amazonian fruit. Journal of Food Science, 82(5), 1083-1091. [CrossRef]
- 18. Zuo, J., Gao, Y., Bou-Chacra, N., Löbenberg, R. (2014). Evaluation of the DDSolver software applications. BioMed Research International, 2014, 204925. [CrossRef]
- 19. Abdul Rasool, B.K., Mohammed, A.A., Salem, Y.Y. (2021). The optimization of a dimenhydrinate transdermal patch formulation based on the quantitative analysis of in vitro release data by DDSolver through skin penetration studies. Scientia Pharmaceutica, 89(3), 33. [CrossRef]
- 20. Mendyk, A., Jachowicz, R., Fijorek, K., Dorozyński, P., Kulinowski, P., Polak, S. (2012). KinetDS: An open source software for dissolution test data analysis. Dissolution Technologies, 19(1), 6-11. [CrossRef]
- 21. Setyaningsih, D., Santoso, Y.A., Hartini, Y.S., Murti, Y.B., Hinrichs, W.L.J., Patramurti, C. (2021). Isocratic high-performance liquid chromatography (HPLC) for simultaneous quantification of curcumin and piperine in a microparticle formulation containing Curcuma longa and Piper nigrum. Heliyon, 7(3), E06541. [CrossRef]
- 22. Shingate, P.N., Dongre, P.P., Kannur, D.M. (2013). New method development for extraction and isolation of piperine from black pepper. International Journal of Pharmaceutical Sciences and Research, 4(8), 3165. [CrossRef]
- 23. Yu, Y., Wei, R., Jia, X., Zhang, X., Liu, H., Xu, B., Xu, B. (2022). Preparation of Piper nigrum Microcapsules by Spray Drying and Optimization with Response Surface Methodology. Journal of Oleo Science, 71(12), 1789-1797. [CrossRef]
- 24. Murti, Y.B., Hartini, Y.S., Hinrichs, W.L.J., Frijlink, H.W., Setyaningsih, D. (2019). UV-Vis spectroscopy to enable determination of the dissolution behavior of solid dispersions containing curcumin and piperine. Journal of Young Pharmacists, 11(1), 26-30. [CrossRef]
- 25. Magri, G., Franzé, S., Musazzi, U.M., Selmin, F., Cilurzo, F. (2019). Data on spray-drying processing to optimize the yield of materials sensitive to heat and moisture content. Data in Brief, 23, 103792. [CrossRef]
- 26. Tay, J.B.J., Chua, X., Ang, C., Subramanian, G.S., Tan, S.Y., Lin, E.M.J., Wu, W.Y., Goh, K.K.T., Lim, K. (2021). Effects of spray-drying inlet temperature on the production of high-quality native rice starch. Processes, 9(9), 1557. [CrossRef]
- 27. Gul, O., Dervisoglu, M. (2020). Optimization of spray drying conditions for microencapsulation of Lactobacillus casei Shirota using response surface methodology. European Food Science and Engineering, 1(1), 1-8.
- 28. Fazaeli, M., Emam-Djomeh, Z., Kalbasi Ashtari, A., Omid, M. (2012). Effect of spray drying conditions and feed composition on the physical properties of black mulberry juice powder. Food and Bioproducts Processing, 90(4), 667-675. [CrossRef]
- 29. Brown, C.K., Friedel, H.D., Barker, A.R., Buhse, L.F., Keitel, S., Cecil, T.L., Kraemer, J., Morris, J.M., Reppas, C., Stickelmeyer, M.P., Yomota, C., Shah, V.P. (2011). FIP/AAPS joint workshop report: dissolution/in vitro release testing of novel/special dosage forms. AAPS PharmSciTech, 12(2), 782-794. [CrossRef]
- 30. Tonon, R.V., Brabet, C., Hubinger, M.D. (2008). Influence of process conditions on the physicochemical properties of açai (Euterpe oleraceae Mart.) powder produced by spray drying. Journal of Food Engineering, 88(3), 411-418. [CrossRef]
- 31. Silva, F.E.F., Di-Medeiros, M.C.B., Batista, K.A., Fernandes, K.F. (2013). PVA/polysaccharides blended films: Mechanical properties. Journal of Materials, 2013, 1-6. [CrossRef]
- 32. Tran, T.A.T., Nguyen, H.V.H. (2018). Effects of spray-drying temperatures and carriers on physical and antioxidant properties of lemongrass leaf extract powder. Beverages, 4(4), 84. [CrossRef]
- 33. Dak, M., Verma, R.C., Jaaffrey, S.N.A. (2007). Effect of temperature and concentration on Rheological properties of “Kesar” mango juice. Journal of Food Engineering, 80(4), 1011-1015. [CrossRef]
- 34. van Duong, T., van den Mooter, G. (2016). The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers. Expert Opinion on Drug Delivery, 13(11), 1583-1594. [CrossRef]
- 35. Taheri, A., Atyabi, F., Dinarvnd, R. (2011). Temperature-responsive and biodegradable PVA:PVP k30:Poloxamer 407 hydrogel for controlled delivery of human growth hormone (hGH). Journal of Pediatric Endocrinology and Metabolism, 24(3-4), 175-179. [CrossRef]
- 36. Zhang, Y., Huo, M., Zhou, J., Zou, A., Li, W., Yao, C., Xie, S. (2010). DDSolver: An add-in program for modeling and comparison of drug dissolution profiles. AAPS Journal, 12(3), 263-271. [CrossRef]
- 37. Huang, W., Lee, S.L., Yu, L.X. (2009). Mechanistic approaches to predicting oral drug absorption. The AAPS Journal, 11, 217-224. [CrossRef]
- 38. Stillhart, C., Parrott, N.J., Lindenberg, M., Chalus, P., Bentley, D., Szepes, A. (2017). Characterising drug release from immediate-release formulations of a poorly soluble compound, basmisanil, through absorption modelling and dissolution testing. The AAPS Journal, 19(3), 827-836. [CrossRef]
KURUTMA SICAKLIĞININ KURKUMİN VE PİPERİN ÇÖZÜNMESİNE VE KATI DİSPERSİYON BAZLI MİKROPARTİKÜLLERİN SALINIM KİNETİĞİNE ETKİLERİ: BİR ÖN ÇALIŞMA
Yıl 2023,
, 853 - 863, 20.09.2023
Monica Octaviani Tiara Dewi
,
Dewi Setyaningsih
Öz
Amaç: Kurkuminin farmasötik bir ajan olarak geliştirilmesindeki en büyük zorluklardan biri, oral uygulamadan sonra düşük biyoyararlanımıdır. Kurkumin-piperin'in katı dispersiyon (KD) yaklaşımı kullanılarak birlikte uygulanmasının kurkumin çözünmesini ve biyoyararlanımını artırdığı gösterilmiştir. Püskürtmeli kurutma sırasında işlem sıcaklığının etkisinin anlaşılması, KD preparatlarında çok önemlidir; bu çalışmanın amacı, püskürtmeli kurutucunun giriş sıcaklığının çözünme davranışı ve çözünmenin en uygun kinetik modeli üzerindeki etkisini araştırmaktır.
Gereç ve Yöntem: KD tozu, giriş sıcaklığı değiştirilerek (105°C; 115°C; 125°C) ve taşıyıcı olarak polivinil alkol (PVA) kullanılarak püskürtmeli kurutma yöntemi ile hazırlanmıştır. KD, %30 Curcuma longa ve %10 Piper nigrum ekstraktları kullanılarak hazırlanmıştır. Püskürtmeli kurutma işleminden elde edilen kurutulmuş tozun verimi (%) izlenmiş ve kurkumin ve piperinin çözünme davranışı, çözünme etkinliği (ÇE) değeri kullanılarak analiz edilmiştir. Ayrıca, kurkumin ve piperinin çözünmeden salınım mekanizmasını tanımlayan matematiksel model bir DDSolver yazılımı kullanılarak değerlendirilmiştir.
Sonuç ve Tartışma: Püskürtmeli kurutucuda kurutma sıcaklığının değişimi, C. longa ve P. nigrum ekstresi içeren PVA bazlı KD'nin çözünme davranışını ve % verimini etkilemektedir. Kurkumin ve piperin için kinetik salınımın en ideal matematiksel modeli, çözünme mekanizmasının PVA partikülü ile çevreleyen ortam arasındaki bir boşluktan difüzyon olduğunu gösteren Kuadratik modeldir.
Proje Numarası
007 Penel./LPPM-USD/II/2022
Kaynakça
- 1. Ashraf, K., Mujeeb, M., Ahmad, A., Ahmad, N., Amir, M. (2015). Determination of curcuminoids in Curcuma longa Linn. by UPLC/Q-TOF-MS: An application in turmeric cultivation. Journal of Chromatographic Science, 53(8), 1346-1352. [CrossRef]
- 2. Wan, S., Sun, Y., Qi, X., Tan, F. (2012). Improved bioavailability of poorly water-soluble drug curcumin in cellulose acetate solid dispersion. AAPS PharmSciTech, 13(1), 159-166. [CrossRef]
- 3. Shoba, G., Joy, D., Joseph, T., Majeed, M., Rajendran, R., Srinivas, P.S.S.R. (1998). Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica, 64(4), 353-356. [CrossRef]
- 4. Gorgani, L., Mohammadi, M., Najafpour, G.D., Nikzad, M. (2017). Piperine-The bioactive compound of black pepper: From isolation to medicinal formulations. Comprehensive Reviews in Food Science and Food Safety, 16(1), 124-140. [CrossRef]
- 5. Chopra, B., Dhingra, A.K., Kapoor, R.P., Prasad, D.N. (2017). Piperine and its various physicochemical and biological aspects: A review. Open Chemistry Journal, 3(1), 75-96. [CrossRef]
- 6. Sachin, S., Nirmala, G., Subir, B., Suresh, J., Dushyant, G. (2012). Development and validation of UV spectroscopic method for the quick estimation of gingerol from Zingiber officinale rhizome extract. International Research Journal of Pharmacy, 3(5), 234-237.
- 7. Patil, V., Chauhan, A.K., Singh, R.P. (2014). Optimization of the spray-drying process for developing guava powder using response surface methodology. Powder Technology, 253, 230-236. [CrossRef]
- 8. Cano-Chauca, M., Stringheta, P.C., Ramos, A.M., Cal-Vidal, J. (2005). Effect of the carriers on the microstructure of mango powder obtained by spray drying and its functional characterization. Innovative Food Science and Emerging Technologies, 6(4), 420-428. [CrossRef]
- 9. Lee, K.C., Yoon, Y.S., Li, F.Z., Eun, J.B. (2017). Effects of inlet air temperature and concentration of carrier agents on physicochemical properties, sensory evaluation of spray-dried mandarin (Citrus unshiu) beverage powder. Applied Biological Chemistry, 60(1), 33-40. [CrossRef]
- 10. Shi, Y., Wang, J., Wang, Y., Zhang, H., Ma, Y., Zhao, X., Zhang, C. (2018). Inlet temperature affects spray drying quality of watermelon powder. Czech Journal of Food Sciences, 36(4), 316-323. [CrossRef]
- 11. Santhalakshmy, S., Don Bosco, S.J., Francis, S., Sabeena, M. (2015). Effect of inlet temperature on physicochemical properties of spray-dried jamun fruit juice powder. Powder Technology, 274, 37-43. [CrossRef]
- 12. Teera-Arunsiri, A., Suphantharika, M., Ketunuti, U. (2009). Preparation of spray-dried wettable powder formulations of Bacillus thuringiensis-based biopesticides. Journal of Economic Entomology, 96(2), 292-299. [CrossRef]
- 13. Hu, L., Shi, Y., Li, J.H., Gao, N., Ji, J., Niu, F., Chen, Q., Yang, X., Wang, S. (2015). Enhancement of oral bioavailability of curcumin by a novel solid dispersion system. AAPS PharmSciTech, 16(6), 1327-1334. [CrossRef]
- 14. Wang, R., Han, J., Jiang, A., Huang, R., Fu, T., Wang, L., Zheng, Q., Li, W., Li, J. (2019). Involvement of metabolism-permeability in enhancing the oral bioavailability of curcumin in excipient-free solid dispersions co-formed with piperine. International Journal of Pharmaceutics, 561, 9-18. [CrossRef]
- 15. Jumah, R.Y., Tashtoush, B., Shaker, R.R., Zraiy, A.F. (2000). Manufacturing parameters and quality characteristics of spray dried jameed. Drying Technology, 18(4-5), 967-984. [CrossRef]
- 16. Muzaffar, K., Kumar, P. (2017). Spray drying of tamarind pulp: Effect of process parameters using protein as carrier agent. Journal of Food Processing and Preservation, 41(2), e12781. [Crossref]
- 17. Fujita, A., Souza, V.B., Daza, L.D., Fávaro-Trindade, C.S., Granato, D., Genovese, M.I. (2017). Effects of spray-drying parameters on in vitro functional properties of camu-camu (Myrciaria dubia Mc. Vaugh): A typical Amazonian fruit. Journal of Food Science, 82(5), 1083-1091. [CrossRef]
- 18. Zuo, J., Gao, Y., Bou-Chacra, N., Löbenberg, R. (2014). Evaluation of the DDSolver software applications. BioMed Research International, 2014, 204925. [CrossRef]
- 19. Abdul Rasool, B.K., Mohammed, A.A., Salem, Y.Y. (2021). The optimization of a dimenhydrinate transdermal patch formulation based on the quantitative analysis of in vitro release data by DDSolver through skin penetration studies. Scientia Pharmaceutica, 89(3), 33. [CrossRef]
- 20. Mendyk, A., Jachowicz, R., Fijorek, K., Dorozyński, P., Kulinowski, P., Polak, S. (2012). KinetDS: An open source software for dissolution test data analysis. Dissolution Technologies, 19(1), 6-11. [CrossRef]
- 21. Setyaningsih, D., Santoso, Y.A., Hartini, Y.S., Murti, Y.B., Hinrichs, W.L.J., Patramurti, C. (2021). Isocratic high-performance liquid chromatography (HPLC) for simultaneous quantification of curcumin and piperine in a microparticle formulation containing Curcuma longa and Piper nigrum. Heliyon, 7(3), E06541. [CrossRef]
- 22. Shingate, P.N., Dongre, P.P., Kannur, D.M. (2013). New method development for extraction and isolation of piperine from black pepper. International Journal of Pharmaceutical Sciences and Research, 4(8), 3165. [CrossRef]
- 23. Yu, Y., Wei, R., Jia, X., Zhang, X., Liu, H., Xu, B., Xu, B. (2022). Preparation of Piper nigrum Microcapsules by Spray Drying and Optimization with Response Surface Methodology. Journal of Oleo Science, 71(12), 1789-1797. [CrossRef]
- 24. Murti, Y.B., Hartini, Y.S., Hinrichs, W.L.J., Frijlink, H.W., Setyaningsih, D. (2019). UV-Vis spectroscopy to enable determination of the dissolution behavior of solid dispersions containing curcumin and piperine. Journal of Young Pharmacists, 11(1), 26-30. [CrossRef]
- 25. Magri, G., Franzé, S., Musazzi, U.M., Selmin, F., Cilurzo, F. (2019). Data on spray-drying processing to optimize the yield of materials sensitive to heat and moisture content. Data in Brief, 23, 103792. [CrossRef]
- 26. Tay, J.B.J., Chua, X., Ang, C., Subramanian, G.S., Tan, S.Y., Lin, E.M.J., Wu, W.Y., Goh, K.K.T., Lim, K. (2021). Effects of spray-drying inlet temperature on the production of high-quality native rice starch. Processes, 9(9), 1557. [CrossRef]
- 27. Gul, O., Dervisoglu, M. (2020). Optimization of spray drying conditions for microencapsulation of Lactobacillus casei Shirota using response surface methodology. European Food Science and Engineering, 1(1), 1-8.
- 28. Fazaeli, M., Emam-Djomeh, Z., Kalbasi Ashtari, A., Omid, M. (2012). Effect of spray drying conditions and feed composition on the physical properties of black mulberry juice powder. Food and Bioproducts Processing, 90(4), 667-675. [CrossRef]
- 29. Brown, C.K., Friedel, H.D., Barker, A.R., Buhse, L.F., Keitel, S., Cecil, T.L., Kraemer, J., Morris, J.M., Reppas, C., Stickelmeyer, M.P., Yomota, C., Shah, V.P. (2011). FIP/AAPS joint workshop report: dissolution/in vitro release testing of novel/special dosage forms. AAPS PharmSciTech, 12(2), 782-794. [CrossRef]
- 30. Tonon, R.V., Brabet, C., Hubinger, M.D. (2008). Influence of process conditions on the physicochemical properties of açai (Euterpe oleraceae Mart.) powder produced by spray drying. Journal of Food Engineering, 88(3), 411-418. [CrossRef]
- 31. Silva, F.E.F., Di-Medeiros, M.C.B., Batista, K.A., Fernandes, K.F. (2013). PVA/polysaccharides blended films: Mechanical properties. Journal of Materials, 2013, 1-6. [CrossRef]
- 32. Tran, T.A.T., Nguyen, H.V.H. (2018). Effects of spray-drying temperatures and carriers on physical and antioxidant properties of lemongrass leaf extract powder. Beverages, 4(4), 84. [CrossRef]
- 33. Dak, M., Verma, R.C., Jaaffrey, S.N.A. (2007). Effect of temperature and concentration on Rheological properties of “Kesar” mango juice. Journal of Food Engineering, 80(4), 1011-1015. [CrossRef]
- 34. van Duong, T., van den Mooter, G. (2016). The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers. Expert Opinion on Drug Delivery, 13(11), 1583-1594. [CrossRef]
- 35. Taheri, A., Atyabi, F., Dinarvnd, R. (2011). Temperature-responsive and biodegradable PVA:PVP k30:Poloxamer 407 hydrogel for controlled delivery of human growth hormone (hGH). Journal of Pediatric Endocrinology and Metabolism, 24(3-4), 175-179. [CrossRef]
- 36. Zhang, Y., Huo, M., Zhou, J., Zou, A., Li, W., Yao, C., Xie, S. (2010). DDSolver: An add-in program for modeling and comparison of drug dissolution profiles. AAPS Journal, 12(3), 263-271. [CrossRef]
- 37. Huang, W., Lee, S.L., Yu, L.X. (2009). Mechanistic approaches to predicting oral drug absorption. The AAPS Journal, 11, 217-224. [CrossRef]
- 38. Stillhart, C., Parrott, N.J., Lindenberg, M., Chalus, P., Bentley, D., Szepes, A. (2017). Characterising drug release from immediate-release formulations of a poorly soluble compound, basmisanil, through absorption modelling and dissolution testing. The AAPS Journal, 19(3), 827-836. [CrossRef]