Tags

Type your tag names separated by a space and hit enter

Relationship Between Phase Solubility Diagrams and Crystalline Structures During Dissolution of Cimetidine/Cyclodextrin Complex Crystals.
J Pharm Sci. 2020 Jul; 109(7):2206-2212.JP

Abstract

Cyclodextrins (CDs) form complex crystals with drugs and improve physicochemical properties of drugs. However, only few reports have summarized relationships between crystal structures of drug/CD and dissolution behavior. In this study, we developed cimetidine (CIM)/CD complex crystals to achieve sustained drug release and investigated the relationship between the dissolution behavior of CIM/CD complexes and their crystal structures. CIM and 3 types of CDs (α-, β-, and γ-CD) formed a complex crystal when subjected to solvent mixing. The CIM/CD complexes had a highly reduced dissolution rate compared to that of the physical mixture of CIM and CD. β-CD improved the solubility of CIM, whereas γ-CD decreased its solubility. Based on the phase solubility diagram, CIM and α-, β-, and γ-CD indicated A-type positive (AP) and AL deviation, and B-type limited solubility (BS) profiles, respectively. In γ-CD, the saturated concentration of CIM decreased owing to the formation of a low-solubility complex with CIM. CIM/α-CD formed cage-type crystals, and CIM/β-CD and CIM/γ-CD formed channel-type crystals. The dissolution rate constant (k) of CIM/α-CD and CIM/β-CD were 0.045 and 0.04 h-1, respectively. CIM/γ-CD and CIM/β-CD displayed channel-type crystals; however, the channel-type crystals of CIM/γ-CD were stabilized by the presence of additional water molecules.

Authors+Show Affiliations

Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510 Japan.Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510 Japan.Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510 Japan.Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510 Japan. Electronic address: s.510@rs.tus.ac.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32246979

Citation

Shimizu, Shota, et al. "Relationship Between Phase Solubility Diagrams and Crystalline Structures During Dissolution of Cimetidine/Cyclodextrin Complex Crystals." Journal of Pharmaceutical Sciences, vol. 109, no. 7, 2020, pp. 2206-2212.
Shimizu S, Wada-Hirai A, Li Y, et al. Relationship Between Phase Solubility Diagrams and Crystalline Structures During Dissolution of Cimetidine/Cyclodextrin Complex Crystals. J Pharm Sci. 2020;109(7):2206-2212.
Shimizu, S., Wada-Hirai, A., Li, Y., Shimada, Y., Otsuka, Y., & Goto, S. (2020). Relationship Between Phase Solubility Diagrams and Crystalline Structures During Dissolution of Cimetidine/Cyclodextrin Complex Crystals. Journal of Pharmaceutical Sciences, 109(7), 2206-2212. https://doi.org/10.1016/j.xphs.2020.03.029
Shimizu S, et al. Relationship Between Phase Solubility Diagrams and Crystalline Structures During Dissolution of Cimetidine/Cyclodextrin Complex Crystals. J Pharm Sci. 2020;109(7):2206-2212. PubMed PMID: 32246979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relationship Between Phase Solubility Diagrams and Crystalline Structures During Dissolution of Cimetidine/Cyclodextrin Complex Crystals. AU - Shimizu,Shota, AU - Wada-Hirai,Ayako, AU - Li,Yingpeng, AU - Shimada,Yohsuke, AU - Otsuka,Yuta, AU - Goto,Satoru, Y1 - 2020/04/01/ PY - 2019/11/13/received PY - 2020/03/05/revised PY - 2020/03/18/accepted PY - 2020/4/5/pubmed PY - 2020/4/5/medline PY - 2020/4/5/entrez KW - Cimetidine KW - Cyclodextrin KW - Dissolution study KW - Phase-solubility diagrams KW - Polymorph SP - 2206 EP - 2212 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 109 IS - 7 N2 - Cyclodextrins (CDs) form complex crystals with drugs and improve physicochemical properties of drugs. However, only few reports have summarized relationships between crystal structures of drug/CD and dissolution behavior. In this study, we developed cimetidine (CIM)/CD complex crystals to achieve sustained drug release and investigated the relationship between the dissolution behavior of CIM/CD complexes and their crystal structures. CIM and 3 types of CDs (α-, β-, and γ-CD) formed a complex crystal when subjected to solvent mixing. The CIM/CD complexes had a highly reduced dissolution rate compared to that of the physical mixture of CIM and CD. β-CD improved the solubility of CIM, whereas γ-CD decreased its solubility. Based on the phase solubility diagram, CIM and α-, β-, and γ-CD indicated A-type positive (AP) and AL deviation, and B-type limited solubility (BS) profiles, respectively. In γ-CD, the saturated concentration of CIM decreased owing to the formation of a low-solubility complex with CIM. CIM/α-CD formed cage-type crystals, and CIM/β-CD and CIM/γ-CD formed channel-type crystals. The dissolution rate constant (k) of CIM/α-CD and CIM/β-CD were 0.045 and 0.04 h-1, respectively. CIM/γ-CD and CIM/β-CD displayed channel-type crystals; however, the channel-type crystals of CIM/γ-CD were stabilized by the presence of additional water molecules. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/32246979/Relationship_Between_Phase_Solubility_Diagrams_and_Crystalline_Structures_During_Dissolution_of_Cimetidine/Cyclodextrin_Complex_Crystals L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(20)30188-X DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.