Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization

Bajracharya, Rajiv; Lee, Sang Hoon; Song, Jae Geun; Kim, Minkyoung; Lee, Kyeong; Han, Hyo-Kyung

doi:10.3390/pharmaceutics11050206

Cited by 20 publications

(9 citation statements)

References 34 publications

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“…These results confirm the increase in crystallization of the MC carrier observed in the PXRD studies for PM and MS-K (1:0.1), and the decrease in crystallinity of the croscarmellose carrier for MS-K (1:0.3). Similar processes of partial amorphization of EZ have been used to obtain EZ nanoparticles [24] or micro/nanoparticles of poorly soluble drugs [25,26]. However, the inclusion of MS-K (1:0.6) and MS-K (1:0.75) surfactant ratios does not display the endothermic peak attributed to croscarmellose (Figure 3).…”

Section: Differential Scanning Calorimetry (Dsc)mentioning

confidence: 97%

Self-Micellizing Technology Improves the Properties of Ezetimibe and Increases Its Effect on Hyperlipidemic Rats

et al. 2019

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The aim of this work was to develop ezetimibe self-micellizing solid dispersions using Kolliphor® RH40 (MS-K) as a surfactant incorporating ezetimibe (EZ) into the croscarmellose hydrophilic carrier. Different ezetimibe:Kolliphor® ratios were studied to select micellar systems that improve the dissolution properties of ezetimibe. The different formulations were characterized by means of solid state analysis by SEM, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and dissolution studies. These physicochemical studies showed a decrease from the crystalline structure of ezetimibe (EZ) to its amorphous state in the micellar systems (MS-K). A rapid dissolution profile was observed in these micellar systems compared to the drug raw material and physical mixture. Efficacy studies were conducted using a high-fat diet that induced hyperlipidemic rats. The micellar system selected (MS-K 1:0.75) revealed a significant improvement in serum levels of total cholesterol (TC), low-density lipoproteins (LDL), and triglycerides (TG) compared to ezetimibe raw material. The histopathological examination of liver tissue also showed that this micellar system exhibited more beneficial effects on liver steatosis compared to ezetimibe raw material (EZ-RM) and the high-fat diet group (HFD). This study suggests that EZ micellar systems using Kolliphor® RH40 could enhance the antihyperlipidemic effect of ezetimibe and reduce liver steatosis.

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Section: Differential Scanning Calorimetry (Dsc)mentioning

confidence: 97%

Self-Micellizing Technology Improves the Properties of Ezetimibe and Increases Its Effect on Hyperlipidemic Rats

et al. 2019

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“…This result may be explained by better wettability, reduced particle size, and a change in drug crystallinity [ 8 , 26 ]. In general, adding a surfactant to an SD formulation should lower the degree of supersaturation, preventing nucleation and thermodynamic crystal growth, and thus inhibiting drug precipitation while improving drug dissolution [ 27 ]. Given that P407 has the dual function of an amphiphilic surfactant and a polymeric carrier [ 28 ], P407 can form micelles and allocate hydrophobic drugs into the micellar core [ 7 , 26 , 27 ], resulting in improved drug solubility.…”

Section: Resultsmentioning

confidence: 99%

“…In general, adding a surfactant to an SD formulation should lower the degree of supersaturation, preventing nucleation and thermodynamic crystal growth, and thus inhibiting drug precipitation while improving drug dissolution [ 27 ]. Given that P407 has the dual function of an amphiphilic surfactant and a polymeric carrier [ 28 ], P407 can form micelles and allocate hydrophobic drugs into the micellar core [ 7 , 26 , 27 ], resulting in improved drug solubility. Next to P407, PVP K30 achieved the second highest enhancement in drug solubility ( Figure 2 ), which may be due to an increase in wettability, dispersion of drugs in amorphous forms, and inhibition of recrystallization [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

Enhanced Oral Bioavailability of MT-102, a New Anti-inflammatory Agent, via a Ternary Solid Dispersion Formulation

et al. 2022

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This study aimed to develop a solid dispersion (SD) of MT-102, a new anti-inflammatory agent, to improve its oral bioavailability. The ternary SD formulations of MT-102 (a poorly soluble extract of Isatis indigotica and Juglans mandshurica) were prepared using a solvent evaporation method with various drug/excipient ratios. Following that, the effectiveness of various SDs as an oral formulation of MT-102 was investigated using indirubin as a marker component. By forming SDs with hydrophilic polymers, the aqueous solubility of indirubin was significantly increased. SD-F4, containing drug, poloxamer 407 (P407), and povidone K30 (PVP K30) at a 1:2:2 weight ratio, exhibited the optimal dissolution profiles in the acidic to neutral pH range. Compared to pure MT-102 and a physical mixture, SD-F4 increased indirubin’s dissolution from MT-102 by approximately 9.86-fold and 2.21-fold, respectively. Additionally, SD-F4 caused the sticky extract to solidify, resulting in improved flowability and handling. As a result, compared to pure MT-102, the oral administration of SD-F4 significantly improved the systemic exposure of MT-102 in rats. Overall, the ternary SD formulation of MT-102 with a blended mixture of P407 and PVP K30 appeared to be effective at improving the dissolution and oral absorption of MT-102.

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“…Based on solubility studies done by us, Kolliphor P-188 was selected as a polymer, whereas tartaric acid was selected as a pH modifier [8]. Complexes were prepared by the melting method [18][19][20][21][22]. To finalize drug to polymer ratio, Ilo:Kolliphor P-188 was tried in 1:1, 1:2, and 1:3 ratios.…”

Section: Preparation Of Complexesmentioning

confidence: 99%

Formulation and Characterization of Sublingual Tablets of Iloperidone Prepared by Microenvironmental pH Regulated Approach

2020

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Purpose Iloperidone (Ilo) is an antipsychotic drug having low and pH-dependent solubility, hence less bioavailability. Thus, the aim of this study was to prepare and characterize binary (TAPOL B) and ternary complexes (TAPOL T) of drug with Kolliphor P-188 and tartaric acid to improve solubility. Further, sublingual tablets incorporating ternary complex were formulated to improve the dissolution. Methods Preliminary screening studies were conducted to select the acidifying agent and polymer based on saturation solubility studies. Binary and ternary complexes were prepared by the melting method. Complexes were characterized by DSC, powder Xray diffraction (PXRD), FTIR, microenvironmental studies, and in vitro dissolution studies. The sublingual tablets of ternary complexes were prepared by the direct compression method and evaluated for weight variation, disintegration time, and dissolution studies. Results Based on solubility studies, Kolliphor P-188 and tartaric acid were selected as polymer and acidifying agents. DSC studies and FTIR spectra showed the interaction of drugs with polymer and acidifying agents. PXRD spectra showed the crystalline nature of complexes. Microenvironmental studies carried out in pH 6.8 showed a drastic decrease in pH with ternary complex as compared with binary complex. Dissolution studies showed an increase in dissolution, TAPOL T > TAPOL B > drug. The sublingual tablets showed disintegration time < 30 s and more than 80% of a drug released within 10 min. Due to the presence of tartaric acid and polymer, solubility of the drug increases tremendously.Conclusion The present study demonstrates the increase in solubility and release of Iloperidone due to the microenvironmental pH effect from sublingual tablets. Hence, microenvironmental pH modification is a good approach to increase drug solubility and dissolution. Keywords Iloperidone . Tartaric acid . Kolliphor P-188 . Ternary complex . Microenvironmental pH . Sublingual tablets Highlights • Binary and ternary complexes of Ilo were formulated.• Kolliphor P-188 and tartaric acid were optimized as a polymer and an auxiliary agent. • Tartaric acid accelerated the dissolution efficiency of the drug due to pH change. • DC tablets showed ≥ 80% release within 5 min for 12 mg, maximum strength.

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Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization

Cited by 20 publications

References 34 publications

Self-Micellizing Technology Improves the Properties of Ezetimibe and Increases Its Effect on Hyperlipidemic Rats

Self-Micellizing Technology Improves the Properties of Ezetimibe and Increases Its Effect on Hyperlipidemic Rats

Enhanced Oral Bioavailability of MT-102, a New Anti-inflammatory Agent, via a Ternary Solid Dispersion Formulation

Formulation and Characterization of Sublingual Tablets of Iloperidone Prepared by Microenvironmental pH Regulated Approach

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