Tags

Type your tag names separated by a space and hit enter

In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration.
AAPS PharmSciTech. 2018 May; 19(4):1882-1893.AP

Abstract

Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form. To assess the effectiveness of DDASS, six high-permeability drugs were chosen as model drugs, including theophylline (pKa1 = 3.50, pKa2 = 8.60), diclofenac (pKa = 4.15), isosorbide 5-mononitrate (pKa = 7.00), sinomenine (pKa = 7.98), alfuzosin (pKa = 8.13), and metoprolol (pKa = 9.70). A general elution and permeation relationship of their commercially available extended-release tablets was assessed as well as the relationship between the cumulative permeation and the apparent permeability. The correlations between DDASS elution and USP apparatus 2 (USP2) dissolution and also between DDASS permeation and beagle dog absorption were developed to estimate the predictability of DDASS. As a result, the common elution-dissolution relationship was established regardless of some variance in the characteristic behavior between DDASS and USP2 for drugs dependent on the pH for dissolution. Level A in vitro-in vivo correlation between DDASS permeation and dog absorption was developed for drugs with different pKa. The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development.

Authors+Show Affiliations

Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin, 300193, People's Republic of China. Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Hebei District, Tianjin, 300250, People's Republic of China.Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Hebei District, Tianjin, 300250, People's Republic of China.Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin, 300193, People's Republic of China.Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin, 300193, People's Republic of China.Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin, 300193, People's Republic of China.Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin, 300193, People's Republic of China.Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin, 300193, People's Republic of China. hexintn@163.com. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, 300193, People's Republic of China. hexintn@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29663288

Citation

Li, Zi-Qiang, et al. "In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets Via Drug Dissolution/Absorption Simulating System and pH Alteration." AAPS PharmSciTech, vol. 19, no. 4, 2018, pp. 1882-1893.
Li ZQ, Tian S, Gu H, et al. In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration. AAPS PharmSciTech. 2018;19(4):1882-1893.
Li, Z. Q., Tian, S., Gu, H., Wu, Z. G., Nyagblordzro, M., Feng, G., & He, X. (2018). In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration. AAPS PharmSciTech, 19(4), 1882-1893. https://doi.org/10.1208/s12249-018-0996-1
Li ZQ, et al. In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets Via Drug Dissolution/Absorption Simulating System and pH Alteration. AAPS PharmSciTech. 2018;19(4):1882-1893. PubMed PMID: 29663288.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration. AU - Li,Zi-Qiang, AU - Tian,Shuang, AU - Gu,Hui, AU - Wu,Zeng-Guang, AU - Nyagblordzro,Makafui, AU - Feng,Guo, AU - He,Xin, Y1 - 2018/04/16/ PY - 2018/01/24/received PY - 2018/03/16/accepted PY - 2018/4/18/pubmed PY - 2018/9/4/medline PY - 2018/4/18/entrez KW - USP apparatus 2 (USP 2) KW - drug dissolution/absorption simulating system (DDASS) KW - dynamic pH change KW - extended-release tablets KW - in vitro-in vivo correlation (IVIVC) SP - 1882 EP - 1893 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 19 IS - 4 N2 - Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form. To assess the effectiveness of DDASS, six high-permeability drugs were chosen as model drugs, including theophylline (pKa1 = 3.50, pKa2 = 8.60), diclofenac (pKa = 4.15), isosorbide 5-mononitrate (pKa = 7.00), sinomenine (pKa = 7.98), alfuzosin (pKa = 8.13), and metoprolol (pKa = 9.70). A general elution and permeation relationship of their commercially available extended-release tablets was assessed as well as the relationship between the cumulative permeation and the apparent permeability. The correlations between DDASS elution and USP apparatus 2 (USP2) dissolution and also between DDASS permeation and beagle dog absorption were developed to estimate the predictability of DDASS. As a result, the common elution-dissolution relationship was established regardless of some variance in the characteristic behavior between DDASS and USP2 for drugs dependent on the pH for dissolution. Level A in vitro-in vivo correlation between DDASS permeation and dog absorption was developed for drugs with different pKa. The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/29663288/In_Vitro-In_Vivo_Predictive_Dissolution-Permeation-Absorption_Dynamics_of_Highly_Permeable_Drug_Extended-Release_Tablets_via_Drug_Dissolution/Absorption_Simulating_System_and_pH_Alteration L2 - https://dx.doi.org/10.1208/s12249-018-0996-1 DB - PRIME DP - Unbound Medicine ER -