Coamorphization combined with complexation enhances dissolution of lurasidone hydrochloride and puerarin with synchronized release

Wang, Shiru; Heng, Weili; Wang, Xiaojie; He, Xin; Zhang, Zefei; Wei, Yuanfeng; Zhang, Jianjun; Gao, Yuan; Qian, Shuai

doi:10.1016/j.ijpharm.2020.119793

Cited by 21 publications

(21 citation statements)

References 59 publications

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“…One possible explanation is the formation of a single-phase ternary ASD due to drug–drug and drug–polymer interactions. A similar phenomenon has been observed in coamorphous systems that revealed a synchronized release profile, while the APIs in a PM dissolved independently. , The synchronized release of multiple therapeutic agents is warranted in several situations, for example, with antigens and adjuvants, active reagents with messengers, and in synergistic formulations …”

Section: Resultsmentioning

confidence: 99%

Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations

Duggirala

Kumar

et al. 2022

Mol. Pharmaceutics

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Using sulfamethoxazole (SMZ) and trimethoprim (TMP) as model drugs, we designed amorphous solid dispersions (ASDs) for the simultaneous solubility enhancement of two active pharmaceutical ingredients (APIs) by exploiting the drug–drug and drug–polymer interactions. In order to make this approach broadly applicable and over a wide dose range, a mixture of SMZ and TMP at weight ratios of 5:1 and 1:5 (w/w) were formulated into ternary ASDs. Depending on the dose ratio of the two drugs, the polymer used was either an aminoalkyl methacrylate copolymer (Eudragit, EDE) or polyacrylic acid. The drug–drug and drug–polymer interactions were characterized to be ionic by infrared and solid-state nuclear magnetic resonance spectroscopy. The interactions resulted in a substantial reduction in molecular mobility, evident from the increase in the structural relaxation time determined by dielectric spectroscopy. The drug–drug interaction resulted in ∼3 orders of magnitude reduction in molecular mobility. The addition of a polymer led to a further decrease in molecular mobility of up to 4 orders of magnitude. The strength of intermolecular interactions was also estimated from the glass transition temperatures of the ASDs obtained by differential scanning calorimetry. The strong intermolecular interactions yielded highly stable ASDs with no evidence of crystallization, both at elevated temperatures and under accelerated storage conditions (40 °C/75% relative humidity; 6 weeks). The dissolution performances of the ASDs were evaluated using the area under the curve (AUC) obtained from the concentration–time profiles under the non-sink condition. SMZ and TMP in their ternary ASDs, when compared with their crystalline counterparts, exhibited up to 6.4- and 4.6-fold increases in AUC, respectively. Importantly, the synchronized release of the two drugs was observed, a desirable attribute in synergistic formulations. A single-phase ternary ASD, stabilized by drug–drug and drug–polymer interactions, is likely responsible for the unique release profile.

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Section: Resultsmentioning

confidence: 99%

Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations

Duggirala

Kumar

et al. 2022

Mol. Pharmaceutics

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“…For example, coamorphous puerarin−lurasidone hydrochloride showed significant dissolution rates of two components as well as a synchronized release behavior in pH 2.0 HCl medium and water at 37 °C (Figure 6), which was mainly attributed to the complex formation between drugs. 65 Besides, coamorphous systems of naproxen with cimetidine, 123 naproxen with indomethacin, 124 and indomethacin with febuxostat 125 also exhibited similar synchronized release phenomena, owing to the formed heterodimer structure through noncovalent interactions.…”

Section: Intrinsic Dissolution Ratementioning

confidence: 96%

“…The supersaturation of puerarin and lurasidone hydrochloride generated from the coamorphous solid was able to be kept for at least 12 h without the decrease to the equilibrium solubility of the physical mixture. 65 On the other hand, during supersaturated dissolution of amorphous materials, a liquid−liquid phase separation (LLPS) phenomenon may take place when the amorphous solubility is exceeded. 117 In the region above solubility of the amorphous phase, either LLPS or crystallization will occur because both processes can reduce its high free energy.…”

Section: Improved Pharmaceutical Properties Of Tcmmentioning

confidence: 99%

“…17 In addition, Wang et al found that coamorphous formulation of puerarin and lurasidone hydrochloride exhibited no crystallization for at least 60 days during storage under 25 °C/60% RH and 40 °C/75% RH, and for at least 12 h during dissolution in aqueous solution, in comparison to both pure amorphous forms of components. 65 4.3.2. Chemical Stability.…”

Section: Stability 431 Physical Stabilitymentioning

confidence: 99%

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Insights into Cocrystallization and Coamorphization Engineering Techniques in the Delivery of Traditional Chinese Medicine: Formation Mechanism, Solid-State Characterization, and Improved Pharmaceutical Properties

Song

Han

et al. 2022

Crystal Growth & Design

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Many active ingredients from traditional Chinese medicine (TCM) exhibit poor pharmaceutical properties (e.g., low aqueous solubility, slow dissolution, low bioavailability, poor stability, and high hygroscopicity, etc.), which are closely associated with various formulation performance issues. Cocrystals or coamorphous systems, incorporating drug and guest molecules into a homogeneous single crystalline or amorphous phase, have been shown to offer potential advantages in enhancing pharmaceutical properties of TCM. This review outlines the definition, classification, preparation methods, characterization techniques, and pharmaceutical properties (such as solubility, dissolution, stability, mechanical properties, permeability, and in vivo performance) of cocrystals and coamorphous systems. More insights into the formation mechanisms of cocrystals and coamorphous systems, the identification of single-phase homogeneous coamorphous systems, and the characterization of their intermolecular interactions between components are covered. Latest research studies on the delivery of TCM via cocrystallization and coamorphization technologies are also summarized. The mechanisms of enhancement in druggability-related properties through cocrystals and coamorphous systems are further discussed. In particular, several common kinetic solubility behaviors of cocrystal and coamorphous systems, including "spring and parachute" and "spring and hover" models, are deeply understood, which will contribute to the maintenance of high supersaturation and in vivo bioavailability.

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“…Due to the preventive effect on osteoporosis, extensive attention of researchers has been attracted recently. Some studies have found that puerarin can promote the proliferation and differentiation of osteoblasts, improve alkaline phosphatase activity, and have a good stimulating effect on alkaline phosphatase activity through in vitro culture of human osteoblasts, which may indicate that puerarin has the function of improving osteoblast bone formation [20,21]. Scanning electron microscope observation showed that puerarin extended osteoblasts well on PLGA/TCP/puerarin repair scaffold, could be connected into sheets, cell matrix secretion is normal, cells and cell matrix could cover the surface of the material, and had good biological compatibility.…”

Section: Related Workmentioning

confidence: 99%

Effects of Puerarin Combined with PLGA/TCP/Puerarin on Osteocalcin and Sialoprotein of Mandibular Defects

Guo

Zhang

Mi³

et al. 2022

Contrast Media & Molecular Imaging

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In order to evaluate the effects of puerarin combined with poly lactic-co-glycolic acid (PLGA)/tricalcium phosphate (TCP)/puerarin on osteocalcin and sialoprotein of mandibular defects, the obtained rat jaw cells are analyzed. The surface morphology of osteoblast complex in the scaffold material group and puerarin combined scaffold material group is observed by a scanning electron microscope, and the growth and proliferation of osteoblasts are detected by the Cell Counting Kit-8 (CCK-8) method. Besides, the expression of type-I collagen (COL-I), osteocalcin (OC), and osteopontin (OPN) mRNA and related proteins in osteoblasts are detected by immunocytochemical staining. The results of immunocytochemical staining show that puerarin and PLGA/TCP/puerarin scaffold had significant effects on the expression of COL-I and OC mRNA and related proteins in osteoblasts. The experimental results indicate that puerarin and PLGA/TCP/puerarin can synergistically affect the mRNA and protein expressions of COL-I, OC, and OPN in osteoblasts and have a positive effect on promoting the proliferation activity of osteoblasts.

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Coamorphization combined with complexation enhances dissolution of lurasidone hydrochloride and puerarin with synchronized release

Cited by 21 publications

References 59 publications

Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations

Design of Ternary Amorphous Solid Dispersions for Enhanced Dissolution of Drug Combinations

Insights into Cocrystallization and Coamorphization Engineering Techniques in the Delivery of Traditional Chinese Medicine: Formation Mechanism, Solid-State Characterization, and Improved Pharmaceutical Properties

Effects of Puerarin Combined with PLGA/TCP/Puerarin on Osteocalcin and Sialoprotein of Mandibular Defects

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