Preparation and Characterization of Indomethacin Supramolecular Systems with β-Cyclodextrin in Order to Estimate Photostability Improvement

Cyclodextrins have found wide application in contemporary chemistry, pharmacy and medicine. Because of their unique properties, cyclodextrins are constantly used in research on solubility or stability improvement, as well as other physicochemical properties of medicinal substances. Indomethacin (IND) is a photolabile molecule that also attracts the interest of researchers due to its therapeutic potential and the need to overcome its problematic photosensitivity. Supramolecular complexes of indomethacin with β-cyclodextrin (CD) are already known, and they show greater stability compared to complexes with other types of cyclodextrins. So far, however, the sensitivity to light of physical mixtures and inclusion complexes in the solid phase has not been studied, and their various stoichiometries have not yet been investigated. Due to this fact, the aim of the present study is to obtain supramolecular systems (inclusion complexes and physical mixtures) of indomethacin with three different amounts of β-cyclodextrin. Assessment of the photochemical stability of indomethacin-β-cyclodextrin systems in the solid state is performed in order to find the best correlation between IND stability and the amount of CD. Comparative analysis of physicochemical degradation for stoichiometry systems [CD:IND] = [1:1], [0.5:1] and [0.1:1] is performed by using ultraviolet spectroscopy, transmission—FTIR, reflection—ATR-FTIR infrared spectroscopy and DSC calorimetry

Volatile organic compounds in pharmacy – the range of the problem

The sensitivity and chemical instability of the active pharmaceutical ingredients (API) may result in the formation and emission of volatile substances which affect not only the stability of the medicinal product, but also leads to changes of physicochemical properties, causing negative pharmacologic effects sometimes toxic. For this reason, it is important to conduct routine stability tests, as well as, to determine gaseous degradation products using modern analytical methods, often unconventional. Knowledge of medicinal chemistry, physical chemistry, technology and toxicology is needed to provide a stable form of the drug and its utmost therapeutic effect. Available guidelines on determined volatile organic compounds (VOCs) present in samples of drug substances have been verified , types of VOCs have been specified and classified. Current literature reviewed shows the results of determination of VOCs in active drug compounds and medicinal products, including discussion on various possibilities of their detection and identification. Currently used methods are based on gas chromatography and ion mobility spectrometry IMS.Brak stabilności chemicznej substancji leczniczych może skutkować powstawaniem i emisją substancji o charakterze lotnym oraz wpływać nie tylko na stabilność produktu leczniczego, lecz również prowadzić do zmian jego właściwości fizykochemicznych, wywoływać negatywne efekty farmakologiczne, a czasami również toksyczne. Z tego względu istotne jest rutynowe prowadzenie testów stabilności, jak również oznaczanie gazowych produktów degradacji nowoczesnymi metodami, często niekonwencjonalnymi. Wiedza z zakresu chemii medycznej, chemii fizycznej, technologii postaci leku i toksykologii jest potrzebna, by zapewnić stabilną postać leku i optymalny efekt terapeutyczny. Scharakteryzowano wytyczne dotyczące oznaczanych lotnych związków organicznych (LZO) obecnych w próbkach substancji leczniczych, wyszczególniono rodzaje LZO i ich klasyfikację. Dokonano przeglądu bieżącej literatury opisującej wyniki oznaczeń LZO w substancjach i produktach leczniczych oraz omówiono różne możliwości ich detekcji i identyfikacji. Obecnie najczęściej wykorzystuje się metody oparte o chromatografię gazową, GC oraz spektroskopię mobilności jonowej, IMS

Volatile organic compounds in pharmacy – the range of the problem

The sensitivity and chemical instability of the active pharmaceutical ingredients (API) may result in the formation and emission of volatile substances which affect not only the stability of the medicinal product, but also leads to changes of physicochemical properties, causing negative pharmacologic effects sometimes toxic. For this reason, it is important to conduct routine stability tests, as well as, to determine gaseous degradation products using modern analytical methods, often unconventional. Knowledge of medicinal chemistry, physical chemistry, technology and toxicology is needed to provide a stable form of the drug and its utmost therapeutic effect. Available guidelines on determined volatile organic compounds (VOCs) present in samples of drug substances have been verified , types of VOCs have been specified and classified. Current literature reviewed shows the results of determination of VOCs in active drug compounds and medicinal products, including discussion on various possibilities of their detection and identification. Currently used methods are based on gas chromatography and ion mobility spectrometry IMS

Light-sensitive medicinal compounds – the actual review of studies and strategies in proceedings

The main procedure for stability testing of Active Pharmaceutical Ingredients (API) and medicinal products is described in the guidelines of the International Council for the Harmonization of Technical Requirements for Human Drugs (ICH). However, these guidelines do not contain specific procedures and methodologies that must be followed in stress testing, especially photostability tests. On the basis of the latest, current research reports which have been published, as well as scientific literature this article provide current information about photolabile medicinal compounds, the structure and properties of their degradation products, as well as various strategies of proceedings. The ICH Q1B guidelines cover two main types of tests, namely 'forced degradation' and 'confirmatory' tests for medicinal products and medical devices and supplements. Forced degradation studies are used to explain the mechanisms of photodegradation and to develop procedures for the proper production, packaging, storage, clinical / production use of the active pharmaceutical ingredient and the final product. These studies are also aimed at developing an appropriate analytical method capable of visualizing potential changes occurring in the medicinal product or demonstrating the specificity of an already existing method. The "confirm" test, as the name suggests, is intended to confirm that the recommended storage conditions and packaging of the medicine are adequate and sufficient to protect the medicinal product. Light exposure for confirmatory testing roughly reflects exposure to typical ultraviolet and visible light for 3 months in case of a medicinal product without protective packaging in a pharmacy, warehouse or home (in the United States / Northern Europe). Therefore, for geographical locations with a greater number of hours and greater sunlight intensity, this period is much shorter. Such test guidelines are determined depending on the geographical location (zone) of the country in which they take place. People believe that product they use and eat are safety while most of the society are convinced that current guidelines concerning quality evaluation of medicinal products are unified and concentrate on verification of stability through determination by particular tests. The purpose of this review is to discuss with criticism all current recommendations referring to the photostability tests performed for pharmaceutical industry mostly connected with human life as pharmacy. The estimation of all existing and obligatory requirements with their gaps are discussed.Podstawowa procedura przeprowadzania badań trwałości substancji leczniczych i produktów leczniczych opisana jest w wytycznych Międzynarodowej Rady Harmonizacji Wymagań Technicznych dla Leków Stosowanych u Ludzi, tzn. ICH (ang. International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use). Wytyczne te nie zawierają jednak szczegółowych procedur i metodologii eksperymentalnej, których należy przestrzegać podczas przeprowadzania testów stresowych, zwłaszcza dotyczących fotostabilności. Na podstawie najnowszego piśmiennictwa naukowego, w pracy przedstawiono testy i różnorodne badania, które dostarczają informacji o fotolabilnych substancjach leczniczych, strukturze i właściwościach produktów ich degradacji, a także różnych strategiach postępowania

Microscopic and Spectroscopic Imaging and Thermal Analysis of Acrylates, Silicones and Active Pharmaceutical Ingredients in Adhesive Transdermal Patches

Dermal or transdermal patches are increasingly becoming a noteworthy alternative as carriers for active pharmaceutical ingredients (APIs), which makes their detailed physicochemical evaluation essential for pharmaceutical development. This paper demonstrates mid-infrared (FTIR) and Raman spectroscopy with complementary microscopic methods (SEM, optical and confocal Raman microscopy) and differential scanning calorimetry (DSC) as tools for the identification of the state of model API (testosterone TST, cytisine CYT or indomethacin IND) in selected adhesive matrices. Among the employed spectroscopic techniques, FTIR and Raman may be used not only as standard methods for API identification in the matrix, but also as a means of distinguishing commercially available polymeric materials of a similar chemical structures. A novel approach for the preparation of adhesive polymers for the FTIR analysis was introduced. In silicone matrices, all three APIs were suspended, whereas in the case of the acrylic PSA, Raman microscopy confirmed that only IND was dissolved in all three acrylic matrices, and the dissolved fraction of the CYT differed depending on the matrix type. Moreover, the recrystallization of TST was observed in one of the acrylates. Interestingly, a DSC analysis of the acrylic patches did not confirm the presence of the API even if the microscopic images showed suspended particles

Physical and Mechanical Evaluation of Silicone-Based Double-Layer Adhesive Patch Intended for Keloids and Scar Treatment Therapy

Growing interest in silicone elastomers for pharmaceutical purposes is due to both their beneficial material effect for scar treatment and their potential as drug carriers. Regarding their morphological structure, silicone polymers possess unique properties, which enable a wide range of applicability possibilities. The present study focused on developing a double-layer adhesive silicone film (DLASil) by evaluating its physical and mechanical properties, morphology, and stability. DLASil suitability for treatment of scars and keloids was evaluated by measurement of tensile strength, elasticity modulus, and elongation. The results indicated that mechanical and physical properties of the developed product were satisfying