Effect of inclusion complexation with cyclodextrins on photostability of nifedipine in solid state

Abstract. The aims of this study were to enhance the solubility and dissolution rate of nimodipine (ND) by preparing the inclusion complexes of ND with sulfobutylether-b-cyclodextrin (SBE-β-CD) and 2-hydroxypropyl-b-cyclodextrin (HP-β-CD) and to study the effect of the preparation method on the in vitro dissolution profile in different media (0.1 N HCl pH 1.2, phosphate buffer pH 7.4, and distilled water). Thus, the inclusion complexes were prepared by kneading, coprecipitation, and freeze-drying methods. Phase solubility studies were conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were investigated with differential scanning calorimetry (DSC), Xray diffractometry (X-RD), and Fourier transform infrared spectroscopy (FT-IR). Stable complexes of ND/SBE-β-CD and ND/HP-β-CD were formed in distilled water in a 1:1 stoichiometric inclusion complex as indicated by an A L -type diagram. The apparent stability constants (Ks) were 1334.4 and 464.1 M −1 for ND/SBE-β-CD and ND/HP-β-CD, respectively. The water-solubility of ND was significantly increased in an average of 22-and 8-fold for SBE-β-CD and HP-β-CD, respectively. DSC results showed the formation of true inclusion complexes between the drug and both SBE-β-CD and HP-β-CD prepared by the kneading method. In contrast, crystalline drug was detectable in all other products. The dissolution studies showed that all the products exhibited higher dissolution rate than those of the physical mixtures and ND alone, in all mediums. However, the kneading complexes displayed the maximum dissolution rate in comparison with drug and other complexes, confirming the influence of the preparation method on the physicochemical properties of the products.

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“…5 a and b, respectively. Similar observations have been reported by other authors [37][38][39]. As shown in Fig.…”

Section: X-ray Diffractometrysupporting

confidence: 93%

Effects of the Preparation Method on the Formation of True Nimodipine SBE-β-CD/HP-β-CD Inclusion Complexes and Their Dissolution Rates Enhancement

et al. 2014

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“…The photodegradation of solid NIF has been reported to follow first-order kinetics. 4,5) Degradation kinetics was calculated according to the following equation:…”

Section: Discussionmentioning

confidence: 99%

“…NIF is photochemically unstable, yielding the following two major photoproducts: nitroso and nitro derivatives. [3][4][5][6] These photodegraded products exert weak (approximately 10000 less potent than NIF) blocking action on voltage-dependent Ca 2+ channels. 7) Thus, improvement of photostability is a key consideration in the development of potent NIF formulations.…”

mentioning

confidence: 99%

Photostable Solid Dispersion of Nifedipine by Porous Calcium Silicate

Fujimoto

Hirai

Takatani‐Nakase

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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Nifedipine (NIF) is a typical light-sensitive drug requiring protection from light during manufacture, storage, and handling of its dosage forms. The purpose of this study was to evaluate the utility of porous calcium silicate (PCS) for maintaining the photostability of NIF in a solid dispersion formulation. Adsorption solid dispersion (ASD) prepared using NIF and PCS as an amorphous formulation was more stable to light irradiation than a physical mixture of NIF and microcrystalline cellulose (a control physical mixture) as a crystalline formulation. In addition, PCS in physical mixtures with NIF adequately protected NIF from photodegradation, suggesting that this protective effect could be because of some screening effect by the porous structure of PCS blocking the passage of light reaching NIF in pores of PCS. These findings suggest that PCS is useful for improving the solubility and photostability of NIF in solid dispersion formulation.

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“…It belongs to a group of active substances with therapeutic use as calcium channel blockers and coronary vasodilators [1][2][3][4][5]. o-Nitro derivatives of 1,4-dihydropyridine are very unstable compounds, which readily oxidize under the influence of light to the nitroso and nitro derivatives shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

“…The limiting factors for the use of nifedipin for clinical purposes are its high photosensitivity and poor solubility [2].…”

Section: Introductionmentioning

confidence: 99%

The protection of Nifedipin from photodegradation due to complex formation with β-cyclodextrin

et al. 2010

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Abstract:The inclusion complex b-cyclodextrin:nifedipin was prepared in solid state by coprecipitation with 1:1 mol ratio. The structure of the obtained complex and nifedipin was characterized by use of X-ray diffraction (XR), infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and differential scanning calorimetry (DSC) methods. The photodegradation of nifedipin and the b-cyclodextrin:nifedipin inclusion complex in solid state was monitored under natural daylight by infrared spectroscopy, whereby the free nifedipin degraded four to five times faster than the complexed nifedipin. The photodegradation products of both free and complexed nifedipin, formed during irradiation at 350 nm (with corresponding energy flux of 18 W m -2 ) were monitored by liquid chromatography during various time intervals. The speed of formation of nitroso-and nitro-phenyl derivatives by nifedipin irradiation was significantly higher than those of complexed nifedipin irradiation, which indicates its increased photostability in the inclusion complex. The effect on this property is significant because it contributes both to the improvement of the therapeutic effect of nifedipin and to the safer application thereof.

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Effect of inclusion complexation with cyclodextrins on photostability of nifedipine in solid state

Cited by 85 publications

References 13 publications

Effects of the Preparation Method on the Formation of True Nimodipine SBE-β-CD/HP-β-CD Inclusion Complexes and Their Dissolution Rates Enhancement

Effects of the Preparation Method on the Formation of True Nimodipine SBE-β-CD/HP-β-CD Inclusion Complexes and Their Dissolution Rates Enhancement

Photostable Solid Dispersion of Nifedipine by Porous Calcium Silicate

The protection of Nifedipin from photodegradation due to complex formation with β-cyclodextrin

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