Compatibility Study of Four Binary Combinations of Active Ingredients for Dermal Film Forming Systems

Abstract

Adapalene (ADA), levofloxacin (LEV), meloxicam (MEL) and miconazole nitrate (MIC) were selected as potential active ingredients for film systems with dermal or transdermal delivery. This study aimed to evaluate the compatibility of four binary mixtures-ADA and LEV (M1), ADA and MIC (M2), LEV and MEL (M3), and LEV and MIC (M4)combinations for new bioadhesive polymeric matrix dermal systems produced by the casting solvent evaporation technique. The Fouriertransform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and molecular modelling (MM) were used to characterise and evaluate the compatibility between the selected active substances. In the FTIR data, M1, M2, and M4 mixtures presented a good compatibility. DSC revealed different chemical interactions as the temperature rose above 160°C, especially for M3 and M4. Through MM technique, interactions were found on the M2 and M3 mixtures. Following the correlation of all obtained results, the best compatibility was found to be on M1 and M4 combinations. Rezumat Adapalenul (ADA), levofloxacina (LEV), meloxicamul (MEL) şi nitratul de miconazol (MIC) au fost selectate ca potenţiale ingrediente active în sistemele de tip film cu eliberare dermică sau transdermică. Scopul acestui studiu este de a evalua compatibilitatea a patru amestecuri binare-ADA şi LEV (M1), ADA şi MIC (M2), LEV şi MEL (M3), şi LEV şi MIC (M4)-combinaţii pentru noi sisteme dermice de tip matriţă polimerică bioadezivă produse prin tehnica de turnare şi evaporare a solventului. Pentru a caracteriza şi evalua compatibilitatea dintre substanţele active selectate au fost utilizate spectroscopia cu transformată Fourier (FTIR), calorimetria cu scanare diferenţială (DSC) şi modelarea moleculară (MM). Din datele FTIR, amestecurile M1, M2 şi M4 au fost compatibilite. DSC a arătat diferite interacţiuni chimice, în special pentru M3 şi M4, la temperaturi mai mari de 160°C. Prin metoda MM au fost semnalate interacţiuni în combinaţiile M2 şi M3. Ca urmare a corelării tuturor rezultatelor obţinute, cea mai bună compatibilitate a fost găsită în combinaţiile M1 şi M4.

Polymeric Films Containing Tenoxicam as Prospective Transdermal Drug Delivery Systems: Design and Characterization

“…Even if the thermal behavior of the physical mixture could be associated with the interactions between the TX and the two polymers, it cannot be stated with certainty. The peak deviations of the TX in DSC thermograms of the analyzed physical mixtures can be explained by the changes in some of its properties, such as the transition from the crystalline form to the amorphous form, an assumption supported by the data from the literature [29].…”

“…Modification or disappearance of an endo-or exothermal peak indicates a possible incompatibility. Frequently, a thermal shift of a characteristic peak may be observed, explained by strong interactions among drug and excipient, but this is not necessarily an incompatibility [28,29]. This explains the necessity of acquiring thermal behavior data with alternative methods, preferably non-thermal, such as Fourier-transform infrared spectrometry [30].…”

Implementation of Experimental Design Methodology in the Compatibility Study of Hydrocortisone With Selected Excipients Used in Solid Dosage Forms

“…A non-accidental selection of a combination of input variables enables the collection of as much information as possible about the formulation with a minimum number of experiments, thus reducing the time and cost of research studies. Thanks to the DoE methodology, research work is carried out in an orderly and thought-out manner, and not in an intuitive way, using the trial and error approach [5,11,18,20,22]. The subject undertaken at this work is completely in accordance with the current trends in modern industrial pharmacy.…”

Evaluating the Capacity of Human Serum Albumin to Reduce Non-Specific Binding of Meloxicam in the Ultrafiltration Process

“…In the present study, we aimed to assess whether a human serum albumin solution has the capacity to reduce NSB using meloxicam (MXC) and piroxicam (PXC) as reference substances. MXC and PXC are both non-steroidal anti-inflammatory drugs [25,26] that have a high affinity for plasma proteins, especially albumin [4,18,19,27,31]. The interaction between meloxicam and HSA is strong in nature, occurring at a single site with high affinity, which is found in the IIA sub-domain and has an association constant of the order of 10 5 M -1 [27,31,32].…”