Crystal forms and bioavailability of erythromycin

Laine, E.; Kahela, P; Rajala, Riitta; Heikkilä, Terttu; Saarnivaara, K.; Piippo, Ilse

doi:10.1016/0378-5173(87)90094-9

Cited by 12 publications

(13 citation statements)

References 4 publications

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“…A number of studies on these forms have been reported. [4][5][6][7][8][9][10][11] At the same time, a literature review showed that similar information on commercially marketed lots of Em raw material is often lacking, and significant variations in the physical properties of the bulk drug are encountered among material supplied by some manufacturers and among different lots supplied by the same manufacturer. 6 Additionally, the intricate molecular structure of Em (Figure 1) suggests the variety of possible supramolecular motifs in crystals, resulting in the formation of different polymorphic modifications.…”

Section: -3mentioning

confidence: 99%

Influence of solvents on the variety of crystalline forms of erythromycin

Mirza¹,

Miroshnyk²,

Heinämäki³

et al. 2003

AAPS PharmSci

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Section: -3mentioning

confidence: 99%

Influence of solvents on the variety of crystalline forms of erythromycin

Mirza¹,

Miroshnyk²,

Heinämäki³

et al. 2003

AAPS PharmSci

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“…7,8) There are many studies in which the behavior of the crystal water molecule is influenced by relative humidity.…”

Section: -4)mentioning

confidence: 99%

“…6) Moreover, the reduction in bioavailability may occur as the solubility of hydrate in general is lower than that of anhydrous form. 7,8) There are many studies in which the behavior of the crystal water molecule is influenced by relative humidity. 9,10) A compound tends to incorporate a water molecule in the crystal structure at high relative humidities, while a hydrate may release the water molecule from the crystal at low relative humidities.…”

mentioning

confidence: 99%

Water Vapor Adsorption Behavior of Sodium Deoxycholate Anhydrous Forms

Ono

Anzai

Tozuka

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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During pharmaceutical development processes, various investigations of physicochemical properties of a drug substance are conducted in order to guarantee the efficacy and the stability of pharmaceutical products. It is well known that the physicochemical properties of drug substances are changed by influence of water vapor under high and low relative humidity conditions. 2-4)A compound holding stoichiometric solvent molecule incorporated within the crystal lattice is designated a solvate. In particular, when the solvent is water, the compound is termed a hydrate, which is the most common solvate of drug substances.5) Because the investigation of manufacturing and formulation processes are conducted with particular attention to the behavior of drug substance hydrate, the existence of the hydrate state has a major impact on the drug development process.6) Moreover, the reduction in bioavailability may occur as the solubility of hydrate in general is lower than that of anhydrous form. 7,8) There are many studies in which the behavior of the crystal water molecule is influenced by relative humidity.9,10) A compound tends to incorporate a water molecule in the crystal structure at high relative humidities, while a hydrate may release the water molecule from the crystal at low relative humidities. It is therefore very important that the effect of relative humidity on the interconversion between the hydrate and anhydrous forms are investigated.Studies of the process of hydration and dehydration are of significance in order to predict the stability of the drug substance. Many hydrated compounds are stabilized by formation of hydrogen bonding networks between water and the drug substance molecule. A hydrated crystal is easily broken by heating and also upon storage at low relative humidities, leading to possible transformation into the anhydrous form by crystal lattice rearrangement. As a result, the drug substance may form the metastable state.Many hydrates of drug substances have been reported, for instance, carbamazepine, 11) theophylline, 12) tetracaine hydrochloride, 13) levofloxacin, 14) and diclofenac acid salts. 15)Among them, the hydrated form exists in several possible hydration states. Tetracaine hydrochloride has hemi-, mono-, and tetrahydrate states, nafagrel hydrochloride has hemi-and monohydrate states, and norfloxacin has sesqui-and pentahydrate states. 16)Sodium deoxycholate (NaDC) containing steroid skeleton is a kind of cholic acid salts. It is known that NaDC forms a micelle, 17) gel, 18) and complex 19) with drugs. It is a white powder used as a supportive solubilizing agent in pharmaceutical formulation. D'Archivio et al. suggested the possibility that NaDC was stabilized by the formation of a tetrahydrate helix structure of NaDC with the four water molecules held rigid by the formation of ion-ion, ion-dipole interactions and hydrogen bonding. 20) Vold et al. presumed the existence of NaDC octahydrate by the investigation of the solubility curve of NaDC.21) However, their findings could not sufficie...

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“…An exotherm with a peak maximum at 155°C is due to crystallization of erythromycin anhydrate from the dehydrate melt. The melting of the anhydrate takes place at ∼190°C 13,14. Therefore, the Raman spectra acquired over the temperature range of 23–195°C (Fig.…”

Section: Resultsmentioning

confidence: 99%