Compatibility of active substances with auxiliary substances in medicinal products

State University of Medicine and Pharmacy "Nicolae Testemiteanu" Chișinău, Republic of Moldova, Congresul consacrat aniversării a 75-a de la fondarea Universității de Stat de Medicină și Farmacie „Nicolae Testemițanu” din Republica Moldova, Ziua internațională a științei pentru pace și dezvoltareIntroduction. Nowadays, auxiliary substances play an important role in the release of the active substance from the pharmaceutical form, through their ability to alter the bioavailability of the active substance. The main reason for the change in bioavailability is the chemical interaction between the ingredients in the “active substance - excipient" system by formation of complexes of polymers, micelles, associates of micelles, macromolecules, chemisorption, etc. Therefore active ingredient must be compatible with the auxiliary substances, which can be tested by Differential scanning calorimetry (DSC), FT-IR spectroscopy studies, High-performance liquid chromatography (HPLC). Purpose. The purpose of the present study was to evaluate physicochemical factors and their impact in the selection process of auxiliary substances for the development of medicinal products. Material and methods. Analyzing the studies of different bibliographic bases, it was found that excipients are not an indifferent mass used in a purely technological aim. For example, the amphetamine in combination with carboxymethylcellulose is practically not absorbed and, accordingly, no pharmacological effect is provided. Phenobarbital in polyethylene glycol is poorly soluble and, as a result, is not absorbed. To improve the dissolution rate of drugs formulated in solid dispersions (example: Piroxicam, Norfloxacin, Nifedipine, Ibuprofen) it is recommended to use polyethylene glycol with different molecular weight. Differential scanning calorimetry is one of the most common methods in order to analyze interactions between components in the formulation. The enthalpy and melting point of different formulations were measured by DSC-60 (Perkin Elmer, Netherlands). Samples (3-5 mg) were accurately weighed to 0.01 mg and placed in aluminum pans then the lids were crimped using a Perkin Elmer crimper. The scanning rate was 10°C min-1 and the range of the temperature was 30 -300°C. The indium standard was used to calibrate the instrument. Results The thermogram of pure spironolactone (SP) showed a sharp endothermic peak at 212°C that indicated the purity of spironolactone. This peak might also indicate melting of the drug. This sharp endothermic peak of spironolactone was disappeared in the thermograms of SP in the liquid vehicle with PEG 400 and glycerin respectively. Thermograms showed that no interactions between SP and excipients have been occurred. Conclusions Due to analysis of the bibliographic studies, it was observed that the effect of excipients on the bioavailability of the active substance is very essential. Therefore it requires a special study, which should ensure the stability, maximum bioavailability and pharmacological action of medicinal products

Compatibilitatea substanțelor active cu cele auxiliare în preparate medicamentoase

Background. Auxiliary substances play an important role in the release of the active substance from the pharmaceutical form, due to their ability to change the drug bioavailability. They must be compatible with the active ingredients, without altering their pharmacological effect. Objective of the study. Comparative evaluation of physico-chemical factors and their impact in the selection process of auxiliary substances for the development of fixed-dose combinations. Material and Methods. Advanced bibliographic study of 71 bibliographic sources from databases: Medline, Scopus, HINARI, PubMed, Cochrane Electronic. Results. The analysis of the evaluated bibliographic sources shows the existence of physico-chemical interactions between the drug and the excipient. About 89% of the authors apply compatibility studies by spectral and thermal methods to detect interactions and select the optimal excipients. To improve the dissolution rate of drugs formulated in solid dispersions (example: Piroxicam, Ibuprofen) it is recommended to use polyethylene glycol with different molecular weight. In most of the evaluated sources (99%) the selection of excipients is made according to the physicochemical properties of the active principles. Conclusion. The research will serve as a basis for developing the method for selecting excipients in the preformulation process of a pharmaceutical product in the form of a polycomponent powder. Introducere. Substanțele auxiliare joacă un rol important în eliberarea substanţei active din forma farmaceutică și ca urmare modifică biodisponibilitatea. Acestea trebuie să fie compatibile cu substanţele active, fără a le modifica efectul farmacologic. Scopul lucrării. Evaluarea comparativă a factorilor fizico-chimici și a impactului acestora în procesul de selectare a substanțelor auxiliare pentru elaborarea produselor farmaceutice combinate. Material și Metode. Studiul bibliografic avansat al 71 surse bibliografice din bazele de date: Medline, Scopus, HINARI, PubMed, Cochrane Electronic. Rezultate. Prin analiza surselor bibliografice evaluate se constată existența interacţiunilor fizico-chimice dintre medicament şi excipient. Circa 89% din autori aplică studiile de compatibilitate prin metode spectrale, termice pentru depistarea interacțiunilor şi selectarea excipienților optimali. Pentru îmbunătățirea ratei de dizolvare a medicamentelor formulate în dispersii solide (ex: Piroxicam, Ibuprofen) se recomandă utilizarea polietilenglicolului cu diferite greutăți moleculare. În majoritatea surselor evaluate (99%) selectarea excipienților se face în funcție de proprietățile fizico-chimice ale principiilor activi. Concluzii. Cercetările efectuate vor servi drept bază pentru elaborarea metodologiei de selectare a excipienților în procesul de preformulare a unui produs farmaceutic sub formă de pulbere policomponentă