Polymorphism of phenylbutazone by a spray drying method

Drugs with low water solubility are predisposed to poor and variable oral bioavailability and, therefore, to variability in clinical response, that might be overcome through an appropriate formulation of the drug. Polymorphs (anhydrous and solvate/hydrate forms) may resolve these bioavailability problems, but they can be a challenge to ensure physicochemical stability for the entire shelf life of the drug product. Since clinical failures of polymorph drugs have not been uncommon, and some of them have been entirely unexpected, the Food and Drug Administration (FDA) and the International Conference on Harmonization (ICH) has required preliminary and exhaustive screening studies to identify and characterize all the polymorph crystal forms for each drug. In the past, the polymorphism of many drugs was detected fortuitously or through manual time consuming methods; today, drug crystal engineering, in particular, combinatorial chemistry and high-throughput screening, makes it possible to easily and exhaustively identify stable polymorphic and/or hydrate/dehydrate forms of poorly soluble drugs, in order to overcome bioavailability related problems or clinical failures. This review describes the concepts involved, provides examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations.

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“…Phenylbutazone is a potent anti-rheumatic drug existing in different polymorphic and solvated forms [110][111][112][113].…”

Section: Phanylbutazonementioning

confidence: 99%

“…Phenylbutazone is a potent anti-rheumatic drug that exists in different polymorphic [110][111][112] and solvated forms [113]. Different solubilities, dissolution rates and oral absorption were highlighted between two different polymorphic forms [114].…”

Section: Phenylbutazonementioning

confidence: 99%

Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs

2015

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“…The preparation and characterization of the phenylbutazone polymorphism have been described previously (9)(10)(11)(12)(13)(14)(15)(16). The preparation and characterization of the phenylbutazone polymorphism have been described previously (9)(10)(11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

Kinetic Study of the Polymorphic Transformations of Phenylbutazone

Matsuda

Tatsumi

Chiba

et al. 1984

Journal of Pharmaceutical Sciences

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“…Phenylbutazone (PBZ) is used as a nonsteroidal anti-inflammatory drug (NSAID) in veterinary medicine. PBZ is known to exist in four different polymorphs (α, β, δ, and Form IV), where Form IV is the most stable . Acetaminophen (AAP), commonly known as Paracetamol, is generally classified as a mild analgesic and is used for the relief of headaches and other minor aches and pains.…”

Section: Introductionmentioning

confidence: 99%

“…PBZ is known to exist in four different polymorphs (α, β, δ, and Form IV), where Form IV is the most stable. 22 Acetaminophen (AAP), commonly known as Paracetamol, is generally classified as a mild analgesic and is used for the relief of headaches and other minor aches and pains. AAP is known to exist in three polymorphic forms (Forms I, II, and III), with Form I being the thermodynamically stable polymorph.…”

Section: Introductionmentioning

confidence: 99%

Crystal Growth Kinetics of Pharmaceutical Compounds

Verma

Lynch

Hodnett

et al. 2020

Crystal Growth & Design

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The crystal growth kinetics of piracetam, fenofibrate, phenylbutazone, acetaminophen, carbamazepine, and risperidone in methanol have been studied by two different methods; the isothermal seeded desupersaturation experiment (ISD) and the rotating disk technique (RD). Data has been collected in the range of temperature 288−303 K and at different supersaturations for the ISD experiments. The RD experiments were performed at constant supersaturation. In the ISD experiments, principal component analysis has been used to relate solution concentrations from IR measurements. An empirical power law equation has been fitted to the experimental desupersaturation data, and parameter values suggest surface integration control for all the APIs studied, a conclusion further supported by a separate mass transfer analysis. The order of rate of growth among the compounds and the magnitude of the growth rates determined by the two methods are in good agreement. In addition, the Burton Cabrera Frank (BCF) and Birth and Spread (B+S) surface integration models have been fitted to the ISD desupersaturation data, and average solid−liquid interfacial energies, mean diffusion distances, and surface mass transport rates have been estimated. An analysis of the experimental results and the growth rate parameters is performed to examine to what extent the difference in growth rate of different compounds can be rationalized.

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Polymorphism of phenylbutazone by a spray drying method

Cited by 18 publications

References 3 publications

Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs

Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs

Kinetic Study of the Polymorphic Transformations of Phenylbutazone

Crystal Growth Kinetics of Pharmaceutical Compounds

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