Physicochemical characterization and compatibility study of roflumilast with various pharmaceutical excipients

Ali, Faraat; Kumar, Ramadhar; Sahu, Puran Lal; Singh, Gyanendra

doi:10.1007/s10973-017-6274-8

Cited by 22 publications

(12 citation statements)

References 22 publications

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“…As current practice in preformulation studies of solid or semisolid dosage forms, the analysis of binary mixtures consisting of equal masses of API and pharmaceutical excipients were also reported for antiviral drug penciclovir [33], ketoconazole [34], atorvastatin calcium [35], rivaroxaban [36], roflumilast [37] or diazepam [38]. Initially, the binary mixtures were subjected to UATR-FTIR analysis in order to evaluate the interactions that may occur under ambient conditions, and later to thermal stress, in order to get an in-depth view for the thermal-induced interactions.…”

Section: Resultsmentioning

confidence: 99%

Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems—Instrumental Screening

et al. 2020

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The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D-mannitol, D-sorbitol, gelatin, calcium lactate pentahydrate, magnesium stearate, methyl 2-hydroxyethyl cellulose (Tylose), colloidal SiO2 (Aerosil) and talc. As investigational tools, universal attenuated total reflectance- Fourier transform infrared spectroscopy UATR-FTIR spectroscopy and thermal analysis were chosen and used as follows: UATR-FTIR spectra were drawn up for samples kept under ambient conditions, while thermoanalytical tools (TG/DTG/HF data) were chosen to evaluate the inducing of interactions during thermal stress. The corroboration of instrumental results led to the conclusion that LTSS is incompatible with lactose, mannitol and sorbitol, and these excipients should not be considered in the development of new generic solid formulations.

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Section: Resultsmentioning

confidence: 99%

Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems—Instrumental Screening

et al. 2020

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“…The roflumilast and maraviroc used in this work have been characterized in the literature. , In this work, the temperatures and enthalpies of fusion of these APIs were measured using DSC and are compared with published literature data in Table . The uncertainties associated with these measurements were estimated using the methods of JCGM .…”

Section: Discussionmentioning

confidence: 99%

Solubility Data for Roflumilast and Maraviroc in Various Solvents between T = (278.2–323.2) K

Moodley

Ramjugernath

2019

J. Chem. Eng. Data

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The solubility at solid–liquid equilibrium (SLE) has been determined for roflumilast (3-(cyclopropylmethoxy)-{N}-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide) in eight solvents and maraviroc (4,4-difluoro-N-[(1S)-3-[(1R,3S,5S)-3-[3-methyl-5-(propan-2-yl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]octan-8-yl]-1-phenylpropyl]cyclohexane-1-carboximidic acid) in nine solvents. Thermal gravimetric analysis with differential thermal analysis was used to obtain compositions at saturation in the temperature range of T = (278.2–323.2) K and at atmospheric pressure. The melting temperatures and enthalpies of fusion of the two solutes were also determined experimentally using a digital scanning calorimeter. The SLE data were adequately correlated by the non-random two-liquid model.

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“…The higher excipient content produce the higher thermal events due to the presence of excipient. Hence, it makes easier detection of potential interactions [13,14].…”

Section: Methodsmentioning

confidence: 99%

Quantification of Compatibility Between Polymeric Excipients and Atenolol Using Principal Component Analysis and Hierarchical Cluster Analysis

2021

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An important challenge to overcome in the solid dosage forms technology is the selection of the most biopharmaceutically efficient polymeric excipients. The excipients can be selected, among others, by compatibility studies since incompatibilities between ingredients of the drug formulations adversely affect their bioavailability, stability, efficacy, and safety. Therefore, new, fast, and reliable methods for detecting incompatibility are constantly being sought. Hence, the purpose of this work was to assess the usefulness of a heating, cooling, and reheating differential scanning calorimetry (DSC) program for detecting potential incompatibilities between atenolol, an active pharmaceutical ingredient (API), and polymeric excipients. Hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (PXRD) were used as supporting techniques. Additionally, principal component analysis (PCA) and hierarchical cluster analysis (HCA) served as tools to support the interpretation of the data acquired from the DSC curves and FTIR spectra. As the alterations in the shape of the DSC peak of atenolol which are indicative of incompatibility are visible only on the cooling and reheating curves of the mixtures, the DSC heating–cooling–reheating program was found to be very useful for identifying potential incompatibilities in the binary mixtures of atenolol and polymeric excipients. The melting and recrystallization of atenolol alone and in its mixtures were also confirmed by HSM, while FTIR displayed changes in the spectra of mixtures due to incompatibility. These studies revealed that atenolol is incompatible with hydroxyethylcellulose, hypromellose, and methylcellulose. PXRD measurements at room temperature revealed that the crystallinity of atenolol did not change in these mixtures. However, its crystallinity was reduced in the mixtures previously heated up to 155 °C and then cooled to 25 °C. Graphical abstract

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Physicochemical characterization and compatibility study of roflumilast with various pharmaceutical excipients

Cited by 22 publications

References 22 publications

Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems—Instrumental Screening

Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems—Instrumental Screening

Solubility Data for Roflumilast and Maraviroc in Various Solvents between T = (278.2–323.2) K

Quantification of Compatibility Between Polymeric Excipients and Atenolol Using Principal Component Analysis and Hierarchical Cluster Analysis

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