Amorphism and Physicochemical Stability of Spray-dried Frusemide

Matsuda, Yoshihisa; Otsuka, Makoto; Onoe, Mika; Tatsumi, Etsuko

doi:10.1111/j.2042-7158.1992.tb05483.x

Cited by 29 publications

(16 citation statements)

References 9 publications

(11 reference statements)

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“…11,12 The moisture sorption/desorption isotherms of the spray-dried and freeze-dried lamotrigine mesylate were essentially identical. The critical moisture content of spray-dried lamotrigine mesylate was 7.6% (SD ) 0.06, n ) 3) at 70-75% RH.…”

Section: Resultsmentioning

confidence: 99%

Moisture-Dependent Crystallization of Amorphous Lamotrigine Mesylate

Schmitt¹,

Davis²,

Long

1996

Journal of Pharmaceutical Sciences

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A commercially available computer-controlled vacuum moisture balance was used for determining moisture sorption isotherms of freeze-dried and spray-dried lamotrigine mesylate drug substance and freeze dried drug product containing mannitol. The presence or absence of desorption hysteresis and the characteristics of the weight-versus-time profile as a sample was exposed to a defined relative humidity ramp were sensitive indicators of moisture-induced crystallization. Combination of the moisture sorption data with polarized light microscopy, differential scanning calorimetry, and X-ray powder diffraction provided qualitative verification of the crystallization with < 50 mg of sample. The normalized water loss during crystallization was used to detect as little as 2% amorphous content in physical mixtures of amorphous and crystalline lamotrigine mesylate. Moisture sorption, water plasticization, and crystallization properties of amorphous forms prepared by spray drying and freeze drying were nearly identical. Cofreeze-drying lamotrigine mesylate with D-mannitol resulted in a mixture of amorphous lamotrigine mesylate with properties similar to those of spray-dried or freeze-dried materials and crystalline D-mannitol. The amount of water needed for crystallization over a time scale observable in the moisture balance was considerably more than the amount needed to lower the glass transition temperature of the sample to the operating temperature of the instrument. This result illustrated the importance of time scale effects in determining critical moisture levels for crystallization from the amorphous state.

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Section: Resultsmentioning

confidence: 99%

Moisture-Dependent Crystallization of Amorphous Lamotrigine Mesylate

Schmitt¹,

Davis²,

Long

1996

Journal of Pharmaceutical Sciences

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“…[22][23][24] As a result of this, the temperature dependence of molecular motions below the glass transition temperature is highly dependent upon the conditions under which the glass was formed. 12 This temperature dependence is generally less extreme than above T g and more linear, with some authors proposing an Arrhenius-like relationship.…”

Section: Definition and Description Of The Amorphous Statementioning

confidence: 98%

Characteristics and Significance of the Amorphous State in Pharmaceutical Systems

Hancock

Zografi

1997

Journal of Pharmaceutical Sciences

1,682

1,053

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The amorphous state is critical in determining the solid-state physical and chemical properties of many pharmaceutical dosage forms. This review describes the characteristics of the amorphous state and some of the most common methods that can be used to measure them. Examples of pharmaceutical situations where the presence of the amorphous state plays an important role are presented. The application of our current knowledge to pharmaceutical formulation problems is illustrated, and some strategies for working with amorphous character in pharmaceutical systems are provided.

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“…Interestingly, Corrigan (1995) has described how changing the spray drying conditions may result in the formation of materials with differing T g values and physical properties. For example, Matsuda et al (1992) prepared amorphous frusemide using two spray drying protocols and reported that the resultant materials had differing T g values (44.2 and 54.4°C). These changes may be a result of differences in moisture content but the study clearly demonstrates the dependence of T g on spray drying protocol.…”

Section: The Physical Stability Of Amorphous Drugsmentioning

confidence: 99%