Solid state evaluation of some thalidomide raw materials

Carini, Juliana Poglia; Pavei, Cabral; Silva, A.P.C.; Machado, Giovanna; Mexias, André Sampaio; Pereira, Vitor Paulo; Fialho, Sílvia Ligório; Mayorga, Paulo

doi:10.1016/j.ijpharm.2008.12.034

Cited by 21 publications

(13 citation statements)

References 23 publications

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“…The crystalline structure of the drug is evidenced in Fig. 6a, which presents characteristic format of big pointed plates, indicating that the raw material is formed mainly by the β polymorph (25). This hypothesis was confirmed by Fourier transformed infrared spectroscopy analysis (data not shown).…”

Section: Preparation and Characterization Of Solid Thalidomide Complexesmentioning

confidence: 59%

“…In vitro dissolution profiles were evaluated as described previously (25), with some modifications, using the USP basket apparatus. Capsules containing 50 mg of thalidomide, or its equivalent in KN or PM products, were added to 1,000 ml of dissolution media (0.225 M HCl and 1% of sodium lauryl sulfate) at 37.0±0.5°C and stirred at 100 rpm on standard dissolution equipment (Nova Ética, Brazil).…”

Section: Dissolution Studiesmentioning

confidence: 99%

“…This variability was attributed to the use of different thalidomide samples and experimental conditions. Raw materials may be composed of different polymorphs and present unrelated dissolution profiles (25). Furthermore, different formulations and dissolution techniques may produce diverse results, as already described (29).…”

Section: Dissolution Studiesmentioning

confidence: 99%

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Preparation, Characterization, and In Vitro Intestinal Permeability Evaluation of Thalidomide–Hydroxypropyl-β-Cyclodextrin Complexes

et al. 2011

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Abstract. Thalidomide is emerging as a therapeutic agent with renewed clinical importance, presenting anti-inflammatory, immunomodulatory, and antineoplasic properties. In this work, we studied the complexation of thalidomide with cyclodextrins as a strategy to circumvent the poor aqueous solubility of the drug. Thalidomide-hydroxypropyl-β-cyclodextrin complexes were obtained by kneading method and were characterized by differential scanning calorimetry, powder X-ray diffractometry, and scanning electronic microscopy. The aqueous solubility and in vitro dissolution of thalidomide were significantly improved through the complexation. Physicochemical analysis of the complexes in solid state revealed a decreased crystallinity of the complexed drug in comparison with free thalidomide. Thalidomide was able to dissociate from the complexes and permeates across intestinal epithelial Caco-2 cells with a favorable high permeability profile equivalent to that of the free drug. In summary, the present results suggest that thalidomide-hydroxypropyl-β-cyclodextrin complexes could be regarded as a promising strategy for improving the gastrointestinal absorption of thalidomide.

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Section: Preparation and Characterization Of Solid Thalidomide Complexesmentioning

confidence: 59%

Section: Dissolution Studiesmentioning

confidence: 99%

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Preparation, Characterization, and In Vitro Intestinal Permeability Evaluation of Thalidomide–Hydroxypropyl-β-Cyclodextrin Complexes

et al. 2011

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“…Polymorphism is often characterized as a drug's ability to exist as two or more crystalline phases that have different arrays, molecular conformations, or both (1,2). Thalidomide ( Figure 1) has two known polymorphic forms, α and β, each one isolated by crystallization using different conditions (3,4).…”

Section: Introductionmentioning

confidence: 99%

Discriminatory Dissolution Test for Tablets Containing a- and b-Thalidomide Polymorphs

Silva¹,

Meneghini²,

Bajerski³

et al. 2013

Dissolution Technol.

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Over the years, thalidomide has been prescribed for an increasing number of diseases, including multiple myeloma and erythema nodosum leprosum. In Brazil and other countries, thalidomide is available in tablets, and there is no official dissolution testing available for this dosage form. Considering this, a dissolution method was developed and validated for tablets containing 100 mg of each polymorph using 1-L vessels to verify that it can differentiate between polymorphs, since drug product is supposed to be formulated with the α form. In addition, the possibility of using smaller volumes of dissolution medium was also explored.This method was compared with the USP dissolution method for thalidomide capsules (4-L vessel) with independent models using difference and similarity factors as well as dissolution efficiency. Dissolution kinetics was evaluated using zero-order, first-order, Higuchi, and Korsmeyer-Peppas models. The kinetic parameters and the suitability of the models for experimental data were evaluated. The developed dissolution method was fully validated. It allowed a better discrimination of thalidomide polymorphs than the USP method for the formulations tested. Considering that it uses a conventional dissolution apparatus with 1-L vessels and there is no method described for tablets, it can be used for quality control of thalidomide in this dosage form.

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“…A discriminative intrinsic dissolution method may indicate the differences that exist between API batches obtained from the same supplier as well as evaluate distinct suppliers of the same API. This would allow monitoring of the quality of raw materials and assist in batch selection of raw materials with physical-chemical properties that are appropriate for formulation development (26)(27)(28)(29).…”

mentioning

confidence: 99%

Development of a Discriminative Intrinsic Dissolution Method for Efavirenz

Pinto¹,

Cabral²,

Sousa³

2014

Dissolution Technol.

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Efavirenz is a poorly water-soluble drug categorized as a Class 2 drug under the Biopharmaceutics Classification System (BCS). Intrinsic dissolution is an effective tool for evaluating the physical-chemical properties of an active pharmaceutical ingredient (API). The aim of this study was to develop an intrinsic dissolution method for use in quality control of efavirenz to be used in the selection of an API for the production of dosage forms. The influence of compression force, rotation speed, dissolution medium, and surfactant concentration on the intrinsic dissolution rate (IDR) of efavirenz were evaluated using a rotating-disk holder. The developed method was applied to the evaluation of batches using different raw materials (batches A-G). Dissolution media containing 0.5% sodium lauryl sulfate (SLS) and a rotation speed of 100 rpm proved the most discriminative. Batches A, D, and F provided intrinsic dissolution rate (IDR) values greater than 36 µg/min/cm 2 in this medium, while batches B and E provided IDR values of approximately 31 µg/min/cm 2 . The IDRs obtained showed a high correlation with the surface areas of the batches. The method may be used in the development of efavirenz formulations to select API with physical-chemical properties that enable appropriate dosage form dissolution.

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Solid state evaluation of some thalidomide raw materials

Cited by 21 publications

References 23 publications

Preparation, Characterization, and In Vitro Intestinal Permeability Evaluation of Thalidomide–Hydroxypropyl-β-Cyclodextrin Complexes

Preparation, Characterization, and In Vitro Intestinal Permeability Evaluation of Thalidomide–Hydroxypropyl-β-Cyclodextrin Complexes

Discriminatory Dissolution Test for Tablets Containing a- and b-Thalidomide Polymorphs

Development of a Discriminative Intrinsic Dissolution Method for Efavirenz

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