A Study of b-Cyclodextrin Inclusion Complexes with Progesterone and Hydrocortisone Using Rotating Frame Overhauser Spectroscopy

Forgó, Péter; Göndös, György

doi:10.1007/s007060270011

Cited by 23 publications

(14 citation statements)

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“…Additionally, 1 H- 1 H 2D ROESY experiments were used to validate through-space intermolecular interactions in the CD inclusion complexes. 45 The interaction of EM011 with β-CD and methyl-β-CD were also demonstrated by using 1 H- 1 H 2D ROESY and are as presented as partial contour plots on Figure 5b and 5c. The correlation between proton H a of 9-Br-Nos and inner proton H 3 of β-CD and methyl-β-CD has been shown.…”

Section: Resultsmentioning

confidence: 89%

Molecular Cycloencapsulation Augments Solubility and Improves Therapeutic Index of Brominated Noscapine in Prostate Cancer Cells

Madan¹,

Baruah

Nagaraju³

et al. 2012

Mol. Pharmaceutics

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We have previously shown that a novel microtubule-modulating noscapinoid, EM011 (9-Br-Nos), displays potent anticancer activity by inhibition of cellular proliferation and induction of apoptosis in prostate cancer cells and preclinical mice models. However, physicochemical and cellular barriers encumber the development of viable formulations for future clinical translation. To circumvent these limitations, we have synthesized EM011-cyclodextrin inclusion complexes to improve solubility and enhance therapeutic index of EM011. Phase solubility analysis indicated that EM011 formed a 1:1 stoichiometric complex with β-CD and methyl-β-CD, with a stability constant (Kc) of 2.42 × 10−3 M and 4.85 × 10−3 M, respectively. Fourier transform infrared spectroscopy suggested the penetrance of either O-CH2 or OCH3-C6H4-OCH3 moiety of EM011 in the β-CD or methyl-β-CD cavity. In addition, multifarious techniques viz., differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, NMR spectroscopy, and computational studies validated the cage complex of EM011 with β-CD and methyl-β-CD. Moreover, rotating frame overhauser enhancement spectroscopy showed that the Ha proton of OCH3-C6H4-OCH3 moiety was in close proximity with H3 proton of β-CD or methyl-β-CD cavity. Furthermore, we found that the solubility of EM011 in phosphate buffer saline (pH 7.4) was enhanced by ∼11 fold and ∼21 fold upon complexation with β-CD and methyl-β-CD, respectively. The enhanced dissolution of the drug CD-complexes in aqueous phase remarkably decreased their IC50 to 28.5 μM (9-Br-Nos-β-CD) and 12.5 μM (9-Br-Nos-methyl-β-CD) in PC-3 cells compared to free EM011 (∼200 μM). This is the first report to demonstrate the novel construction of cylcodextrin-based nanosupramolecular vehicles for enhanced delivery of EM011 that warrants in vivo evaluation for the superior management of prostate cancer.

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Section: Resultsmentioning

confidence: 89%

Molecular Cycloencapsulation Augments Solubility and Improves Therapeutic Index of Brominated Noscapine in Prostate Cancer Cells

Madan¹,

Baruah

Nagaraju³

et al. 2012

Mol. Pharmaceutics

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“…It can thus be concluded that b-cyclodextrin and magnesium stearate are incompatible with hydrocortisone. Hydrocortisone has been found to form an inclusion complex with b-cyclodextrin [19][20][21][22]. Incompatibility of hydrocortisone with magnesium stearate is probably due to interaction of the -OH group of hydrocortisone with the bridging carboxylic group of magnesium stearate via hydrogen bonding involving water, similarly as in the case of captopril and magnesium stearate.…”

Section: Pca and Ca As Supporting Techniquesmentioning

confidence: 99%

Compatibility studies of hydrocortisone with excipients using thermogravimetric analysis supported by multivariate statistical analysis

Rojek

Wesołowski

2016

J Therm Anal Calorim

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Application of thermogravimetry (TG) alone to study compatibility/incompatibility of active pharmaceutical ingredients (APIs) with excipients yields to misleading results due to overlapping of the thermal stages in the course of decomposition of both ingredients and their pharmaceutical mixtures. Hence, the purpose of this study was to assess the usefulness of multivariate statistical analysis as a supporting tool for interpretation of the TG traces during assessing compatibility of hydrocortisone as an API with selected excipients (mannitol, starch, lactose, methylcellulose, b-cyclodextrin, meglumine, chitosan, magnesium stearate and polyvinylpyrrolidone). The results show that two multivariate techniques, principal component analysis (PCA) and cluster analysis (CA), can be successfully used for interpretation of TG traces, while the TG is used alone as a screening technique to assess compatibility. The results obtained by using TG analysis, supported by PCA and CA, were approved by those of differential scanning calorimetry, infrared spectroscopy and X-ray powder diffraction. Incompatibilities were only found in mixtures of hydrocortisone with magnesium stearate and b-cyclodextrin.

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“…Numerous studies of the relationship between the structure of the steroids and the stability of their CD complexes have been conducted 8–14. There is also a growing number of structural studies conducted on CD complexes with steroids and steroid‐related molecules in solution 14–20…”

Section: Introductionmentioning

confidence: 99%

Phase solubility and structure of the inclusion complexes of prednisolone and 6α‐methyl prednisolone with various cyclodextrins

Larsen

Aachmann

Wimmer

et al. 2005

Journal of Pharmaceutical Sciences

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A Study of b-Cyclodextrin Inclusion Complexes with Progesterone and Hydrocortisone Using Rotating Frame Overhauser Spectroscopy

Cited by 23 publications

References 0 publications

Molecular Cycloencapsulation Augments Solubility and Improves Therapeutic Index of Brominated Noscapine in Prostate Cancer Cells

Molecular Cycloencapsulation Augments Solubility and Improves Therapeutic Index of Brominated Noscapine in Prostate Cancer Cells

Compatibility studies of hydrocortisone with excipients using thermogravimetric analysis supported by multivariate statistical analysis

Phase solubility and structure of the inclusion complexes of prednisolone and 6α‐methyl prednisolone with various cyclodextrins

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