Mixing method influence on compatibility and polymorphism studies by DSC and statistical analysis

The physical and chemical characterization of the solid-state properties of drugs and excipients is fundamental for planning new formulations and developing new strategies for the treatment of diseases. Techniques such as differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy are among the most commonly used techniques for these purposes. Penciclovir and lysine are individually used to treat the herpes virus. As such, the development of a formulation containing both drugs may have therapeutic potential. Solid-state characterization showed that both penciclovir and lysine were crystalline materials with melting points at 278.27 °C and 260.91 °C, respectively. Compatibility studies of penciclovir and lysine indicated a possible interaction between these substances, as evidenced by a single melting point at 253.10 °C. The compatibility of several excipients, including ethylenediaminetetraacetic acid, cetostearyl alcohol, sodium lauryl sulphate, di-tert-butyl methyl phenol, liquid petrolatum, methylparaben, nonionic wax, paraffin, propylene glycol, and propylparaben, was evaluated in ternary (penciclovir-lysine-excipient) mixtures (1:1:1, w/w/w) to determine the optimal formulation. The developed formulation was stable under accelerated and ambient conditions, which demonstrated that the interaction between penciclovir and lysine was suitable for the development of a formulation containing both drugs.

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“…The components were vortex mixed (Quimis ® , Diadema, SP, Brazil) for 1 min at 2500 rpm. This mixing procedure promoted homogeneity [27].…”

Section: Methodsmentioning

confidence: 99%

Solid-State Characterization and Compatibility Studies of Penciclovir, Lysine Hydrochloride, and Pharmaceutical Excipients

et al. 2019

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“…Incompatibility is detected by comparing the DSC curves of mixtures with those of individual ingredients [15,17]. Through DSC, information is acquired about the peak temperature, heat, shifts of endothermic or exothermic effects, and the appearance or disappearance of any new ones [5,18]. The visual alterations on the DSC curve of binary mixture and changes in the value of thermodynamic parameters compared to those for the ingredients alone indicate incompatibilities between ingredients.…”

Section: Resultsmentioning

confidence: 99%

“…Hence, to obtain effective and safe pharmaceutical preparations, the selection of excipient is extremely important [3], no less so on account of the presence of "reactive impurities" in the excipient that could contribute to API degradation [4]. As the leading analytical methods in pharmaceutical technology, DSC and TGA are applied for API-excipient compatibility and stability assessment, and quality control of drug formulations [5,6]. DSC allows the rapid screening of possible incompatibilities in drug products by revealing changes in melting endotherms due to the shifting, disappearance of peaks or the appearance of new ones, variations in the values of enthalpy of fusion, and alterations in the decomposition pathway as compared to the separate ingredients [7].…”

Section: Introductionmentioning

confidence: 99%

A combined differential scanning calorimetry and thermogravimetry approach for the effective assessment of drug substance-excipient compatibility

Rojek

Wesołowski

2022

J Therm Anal Calorim

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Differential scanning calorimetry (DSC) is a tool particularly recommended for rapid compatibility screening between active pharmaceutical ingredients (APIs) and excipients, whereas thermogravimetric analysis (TGA), a complementary technique to DSC, is primarily used to assess the thermal stability of APIs and excipients. Both DSC and TGA data can be converted using multivariate statistical methods, which are profitable tools in the detection of compatibility between ingredients. Principal component analysis (PCA) enables identification of compatibility by grouping samples into two clusters in a PCA score plot: acetazolamide and mixture with its highest content, and optionally a 1:1 mixture form one cluster, excipient and mixture with its highest quantity, and optionally a 1:1 mixture the second. Any variation from the arrangement of samples in the abovementioned clusters indicates incompatibility. By using cluster analysis, compatibility can be determined by four clusters, the first consisting of API, the second of groups mixture at the ratio of 7:3 and the third of two mixtures at ratios of 3:7 and 1:1, with the excipient in the remaining fourth cluster. Generally, the combination of DSC and TGA techniques with advanced statistical methods is favorable for the qualitative assessment of compatibility in acetazolamide mixtures with excipients such as mannitol, meglumine, lactose, magnesium stearate, β-cyclodextrin, chitosan, methylcellulose, starch 1500 and PVP K-30. In addition, PXRD revealed that acetazolamide retains its crystalline form after mixing. Accordingly, incompatibilities in acetazolamide mixtures can be attributed to chemical reactions.

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“…This first endothermic peak is then followed by a small exothermic event, which could be attributed to the recrystallization of the melted API into form 1, which has a melting peak at 144.93 ºC (∆H fus =62.82 J g -1 ). 22,23 In the DSC of lactose monohydrate, several endothermic peaks were observed, the first two undifferentiated, around 143ºC, are a consequence of water loss. The third peak at 156.76 ºC could be the anomerization of -lactose to -lactose, due to the presence of residual water.…”

Section: Drug-excipient Compatibility Studies By Dscmentioning

confidence: 99%

Exploring an Industrial Manufacturing Process of a Drug Containing Tenofovir

Pena,

Guillermo,

Sofia

et al. 2024

J. Young Pharm.

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Background: Tenofovir is an antiretroviral drug, a reverse transcriptase inhibitor formulated as tenofovir disoproxil in its saline form, which acts as a prodrug of tenofovir. Its clinical use is indicated in the treatment of Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV). In this work, a solid oral formulation in coated tablets of tenofovir disoproxil has been designed, using an appropriate manufacturing process to overcome any possible problems of stability, compressibility and bioavailability. Materials and Methods: Compatibility studies have been carried out through thermal analysis (Differential Scanning Calorimetry, DSC) and infrared spectroscopy (FT-IR), pharmacotechnical characterization through analysis of flow time, angle of repose, Hausner Ratio and Carr Index, and Pharmacochemical characteristics (weight, hardness, disintegration, thickness and friability). Results: In the pharmaceutical industry, the selection of the most correct tablet production method depends on the individual characteristics of the components and their ability to flow, compress and disintegrate. In this work, a wet granulation process was selected, key to achieving specific granulation, followed by compression and film coating. DSC and FT-IR spectral studies demonstrated that there is no interaction between the active pharmaceutical ingredient and the excipients. Excellent results were found in the pharmacotechnical and physicochemical characterization to obtain the tablets, demonstrating the adequate production process. Conclusion: Tenofovir film coated tablets were successfully formulated using the wet granulation compression method and film coating. The methodologies used demonstrated the appropriate selection of the excipients in terms of physical and chemical compatibility and the suitability of the mixture for use in the process of obtaining the tablet.

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Mixing method influence on compatibility and polymorphism studies by DSC and statistical analysis

Cited by 9 publications

References 20 publications

Solid-State Characterization and Compatibility Studies of Penciclovir, Lysine Hydrochloride, and Pharmaceutical Excipients

Solid-State Characterization and Compatibility Studies of Penciclovir, Lysine Hydrochloride, and Pharmaceutical Excipients

A combined differential scanning calorimetry and thermogravimetry approach for the effective assessment of drug substance-excipient compatibility

Exploring an Industrial Manufacturing Process of a Drug Containing Tenofovir

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