Comparative Effects of (SBE)7m‐β‐CD and HP‐β‐CD on the Stability of Two Anti‐neoplastic Agents, Melphalan and Carmustine

Quintanar‐Guerrero, David; Rajewski, Roger A.; Velde, David Vander; Stella, Valentino J.

doi:10.1002/(sici)1520-6017(200002)89:2<275::aid-jps15>3.0.co;2-c

Cited by 33 publications

(17 citation statements)

References 32 publications

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“…In other words, solubility is low in acidic medium, becoming greater in neutral or alkaline media. This pH-dependent characteristic is a result of the ionization of the carboxylic groups that show a pKa value around 3.5 (Ma et al, 2000).…”

Section: Ionizable Derivativesmentioning

confidence: 99%

Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs

Miranda

Martins

Veiga

et al. 2011

Braz. J. Pharm. Sci.

137

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Cyclodextrins (CDs) are cyclic oligosaccharides composed of D-glucopyranoside units linked by glycosidic bonds. Their main property is the ability to modify the physicochemical and biological characteristics of low-soluble drugs through the formation of drug:CD inclusion complexes. Inclusion complexation requires that host molecules fit completely or partially within the CD cavity. This adjustment is directly related to the physicochemical properties of the guest and host molecules, easy accommodation of guest molecules within the CD cavity, stoichiometry, therapeutic dose, and toxicity. However, dosage forms may achieve a high volume, depending on the amount of CD required. Thus, it is necessary to increase solubilization efficiency in order to use smaller amounts of CD. This can be achieved by adding small amounts of water-soluble polymers to the system. This review addresses aspects related to drug complexation with CDs using water-soluble polymers to optimize the amount of CD used in the formulation in order to increase drug solubility and reduce dosage form volume. Uniterms:Cyclodextrins. Ternary complexes. Drugs/complexation. Water-soluble polymers/use. Drugs/ solubility. Inclusion complexe.Ciclodextrinas (CDs) são oligossacarídeos cíclicos, compostos por unidades D-glicopiranosídicas ligadas entre si por meio de ligações glicosídicas e sua principal propriedade está na capacidade de alterar as características físico-químicas e biológicas de fármacos com baixa solubilidade por meio da formação de complexos de inclusão fármaco:CD. Para a formação dos complexos de inclusão a molécula hospedeira necessita ajustar-se total ou parcialmente no interior da cavidade da CD, onde este ajuste está diretamente ligado a propriedades físico-químicas da molécula hóspede e hospedeira, facilidade de alojamento da molécula hóspede no interior da cavidade da CD, estequiometria, dose terapêutica e toxicidade. No entanto, as formas farmacêuticas podem atingir um elevado volume, em função da quantidade de CD requerida, sendo necessário aumentar sua eficiência de solubilização para que seja possível utilizar menores quantidades das mesmas. Isso pode ser obtido com a inclusão de pequenas quantidades de polímeros hidrossolúveis ao sistema. Nessa revisão, são abordados aspectos relacionados à complexação de fármacos com ciclodextrinas empregando-se polímeros hidrossolúveis para otimização da quantidade de CD utilizada na formulação, com a finalidade de aumentar a solubilidade do fármaco e reduzir o volume das preparações.Unitermos: SCiclodextrinas. Complexos ternários. Fármacos/complexação. Polímeros hidrossolúveis/ uso. Fármacos/solubilidade. Complexos de inclusão.

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Section: Ionizable Derivativesmentioning

confidence: 99%

Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs

Miranda

Martins

Veiga

et al. 2011

Braz. J. Pharm. Sci.

137

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“…Aqueous solubility of cefixime was linearly increased as a function of Captisol concentration with a slope of 0.0154 (r 2 = 0.9853) over the concentration range investigated, suggesting the formation of an A L -type inclusion complex. Since the slope of the phase solubility line was smaller than 1, the formation of 1:1 cefixime-Captisol complex was suggested in an aqueous solution of Captisol (Ma et al 2000;Liu & Zhu 2006). In an aqueous solution of cefixime-Captisol complex, the free drug molecules are in equilibrium with the drug molecules entrapped in the cavity.…”

Section: Phase Solubility and Free Energy Of Transfermentioning

confidence: 99%

Kinetic measurements of the hydrolytic degradation of cefixime: effect of Captisol complexation and water-soluble polymers

Mallick

Mondal

Sannigrahi

2008

Journal of Pharmacy and Pharmacology

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We have taken kinetic measurements of the hydrolytic degradation of cefixime, and have studied the effect of Captisol complexation and water-soluble polymers on that degradation. The phase solubility of cefixime in Captisol was determined. Kinetic measurements were carried out as a function of pH and temperature. High-performance liquid chromatography (HPLC) was performed to assay all the samples of phase-solubility analysis and kinetic measurements. Chromatographic separation of the degradation products was also performed by HPLC. FT-IR spectroscopy was used to investigate the presence of any interaction between cefixime and Captisol and soluble polymer. The phase-solubility study showed A L -type behaviour. The pH-rate profile of cefixime exhibited a U-shaped profile whilst the degradation of cefixime alone was markedly accelerated with elevated temperature. A strong stabilizing influence of the cefixime-Captisol complexation and hypromellose was observed against aqueous mediated degradation, as compared with povidone and macrogol. The unfavourable effect of povidone and macrogol may have been due to the steric hindrance, which prevented the guest molecule from entering the cyclodextrin cavity, whereas hypromellose did not produce any steric hindrance.

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“…Changes in the UV-visible absorption spectrum (shift in the absorption maxima or band) have been observed when a molecule forms inclusion complex with cyclodextrin derivatives (42,44). In the present study, the effect of TA-β-CD on the visible absorption band of anthocyanins was qualitatively investigated by keeping the concentration of the guest constant (RE concentration = 0.1 mg/mL) and by varying the host concentration between 1 to 9 mg/mL for TA-β-CD.…”

Section: Resultsmentioning

confidence: 99%

Formulation and In Vitro-In Vivo Evaluation of Black Raspberry Extract-Loaded PLGA/PLA Injectable Millicylindrical Implants for Sustained Delivery of Chemopreventive Anthocyanins

et al. 2010

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Purpose-The objective of this study was to formulate and evaluate freeze-dried black raspberry (FBR) ethanol extract (RE) loaded poly(DL-lactic-co-glycolic acid) (PLGA) and poly(DL-lactic acid) (PLA) injectable millicylindrical implants for sustained delivery of chemopreventive FBR anthocyanins (cyanidin-3-sambubioside (CS), cyanidin-3-glucoside (CG) and cyanidin-3-rutinoside (CR)).Methods-Identification and quantitation of CS, CG, and CR in RE was performed by mass spectroscopy and HPLC. RE:triacetyl-β-cyclodextrin (TA-β-CD) inclusion complex (IC) was prepared by a kneading method and characterized by X-ray diffraction (XRD), nuclear magnetic resonance spectroscopy (NMR) and UV-visible spectroscopy. RE or RE:TA-β-CD IC-loaded PLGA or PLA implants were prepared by a solvent extrusion method. In vitro and in vivo controlled release studies were conducted in phosphate-buffered saline Tween-80 (pH 7.4, 37°C) and after subcutaneous administration in male Sprague-Dawley rats, respectively. Anthocyanins were quantified by HPLC at 520 nm.Results-The content of CS, CG, and CR in RE was 0.2, 1.5, and 3.5 wt%, respectively. The chemical stability of anthocyanins in solution was determined to be pH-dependent, and their degradation rate increased with an increase in pH from 2.4 to 7.4. PLGA/PLA millicylindrical implants loaded with 5 or 10 wt% RE exhibited a high initial burst and short release duration of anthocyanins (35-52 and 80-100% CG + CR release after 1 and 14 days, respectively). The cause for rapid anthocyanins release was linked to higher polymer water uptake and porosity associated with the high osmolytic components of large non-anthocyanin fraction of RE. XRD, 1 H NMR and UV-visible spectroscopy indicated that the non-anthocyanin fraction molecules of RE formed an IC with TA-β-CD, decreasing the hydrophilicity of RE. Formation of an IC with hydrophobic carrier, TA-β-CD, provided better in vitro/in vivo sustained release of FBR anthocyanins (16-24 and 97-99% CG + CR release, respectively, after 1 and 28 days from 20 wt% RE:TA-β-CD IC/PLA implants) over 1 month, owing to reduced polymer water uptake and porosity.4 To whom correspondence should be addressed. (schwende@umich.edu). Conclusion-PLA injectable millicylindrical implants loaded with RE:TA-β-CD IC are optimal dosage forms for 1-month slow and continuous delivery of chemopreventive FBR anthocyanins. NIH Public Access

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Comparative Effects of (SBE)7m‐β‐CD and HP‐β‐CD on the Stability of Two Anti‐neoplastic Agents, Melphalan and Carmustine

Cited by 33 publications

References 32 publications

Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs

Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs

Kinetic measurements of the hydrolytic degradation of cefixime: effect of Captisol complexation and water-soluble polymers

Formulation and In Vitro-In Vivo Evaluation of Black Raspberry Extract-Loaded PLGA/PLA Injectable Millicylindrical Implants for Sustained Delivery of Chemopreventive Anthocyanins

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