New technological solutions in the aspect of topical and oral administration of resveratrol

Resweratrol (3,4',5-trihydroksystilben) jako substancja o szerokim spektrum aktywności biologicznej stanowi przedmiot wielokierunkowego zainteresowania. Obecnie stosowany jest jako suplement diety oraz składnik kosmetyków o przeciwstarzeniowym działaniu, jednak najnowsze wyniki badań wskazują możliwość rozszerzenia zakresu terapeutycznego resweratrolu m.in. o pielęgnacje ran. Wielokierunkowe działanie farmakodynamiczne, przy jednocześnie trudnej rozpuszczalności w wodzie i niskiej biodostępności rozszerza problematykę badawczą o poszukiwanie nowych form leku zapewniających uzyskanie optymalnego efektu terapeutycznego. Szczególnie obiecujące są układy przeznaczone do aplikacji na skórę, jakkolwiek ciekawa jest też propozycja formulacji do podania drogą doustną. W pracy przedstawiono aktualny stan wiedzy na temat właściwości i zakresu stosowania resweratrolu, ze szczególnym uwzględnieniem nowych rozwiązań technologicznych w formie liposomów, nanoemulsji, nanokryształów, nanocząstek lipidowych czy materiałów opatrunkowych pod kątem jego miejscowego i doustnego podania.Resveratrol (3,5,4-trihydroxystilbene) is a natural polyphenolic compound with a wide spectrum of biological activities, which could possibly be useful in the prevention or treatment of cardiovascular, neurodegenerative diseases, cancer, as well as premature skin aging. The extraction and synthesis methods have been developed rapidly for resveratrol. It is isolated mainly from Polygonum cuspidatumdue to its high concentration in this herb. However, rapid development of biotechnology led to a new way of resveratrol synthesis directly in recombinant yeast, but also in bacteria, such as Escherichia coli.Currently, resveratrol is used as a dietary supplement in form of tablets, capsules or sublingual drops. Nonetheless, resveratrol application is still being a major challenge due to its poor solubility in water as well as low and erratic bioavailability. However, the latest studies showed the possibility of extending the therapeutic range of resveratrol utility, including its potential as a wound care agent. The systems designed for application to the skin are particularly promising, although the formulations proposal for oral administration are also interesting. Despite its potential as a compound administered topically, nowadays resveratrol is available only as an anti-aging ingredient in skin care products. As a substance with the pleiotropic mode of action, it has become the object of interest of many research groups as well as the pharmaceutical industry. Most studies have tended to focus on pharmacological activity of raw resveratrol and its poor bioavailabilty, thus the number of research concerning the development of a drug delivery system for resveratrol is very limited.The present review summarizes the most recent literature which demonstrates the currently used technologies allowing to overcome poor bioavailability of resveratrol, with particular emphasis put on its topical and oral administration. The article shows the current state of knowledge on delivery systems with resveratrol such as liposomes, nanoemulsions, lipid nanoparticles and nanocrystals. It presents also an overview of recent developments in the use of resveratrol in the prevention and treatment of different skin diseases

Orodispersible films (ODF) in individualized therapy

Jednym z czynników wpływających na zapewnienie bezpiecznej i skutecznej farmakoterapii jest opracowanie odpowiedniej postaci leku dostosowanej do wieku pacjenta oraz łatwej w aplikacji, a także urządzeń dozujących umożliwiających dobór odpowiedniej dawki leku. Takie podejście jest zgodne z ideą leczenia skoncentrowanego na pacjencie. Spośród doustnych postaci leku, ze względu na zalety takie jak bezpieczeństwo, łatwość połykania czy możliwość regulacji dawki szczególną uwagę poświęca się postaciom takim jak minitabletki, tabletki i filmy rozpadające się w jamie ustnej. Filmy ODF są wskazywane jako odpowiednia postać leku dla pacjentów pediatrycznych i geriatrycznych ze względu na szybki rozpad w jamie ustnej bez konieczności popijania wodą, przywieranie do błony śluzowej zmniejszając ryzyko wyplucia leku oraz możliwość dostosowania dawki leku dla indywidualnego pacjenta. Według badań filmy ODF są dobrze tolerowane przez dzieci jak również przez opiekunów. Mają postać cienkiego polimerowego płatka umieszczanego na języku. Filmy ODF mogą być wytwarzane przy użyciu różnych metod, tj. wylewania z odparowaniem rozpuszczalnika, ekstruzji topliwej, przędzenia elektrostatycznego, druku (atramentowego, fleksograficznego oraz druku przestrzennego 3D) na skalę przemysłową oraz potencjalnie np. w aptekach szpitalnych. Przygotowywanie filmów ODF ex tempore zapewnia większą możliwość regulacji dawkowania, wpływając na przestrzeganie przez pacjenta zaleceń farmakoterapii. Nowoczesne rozwiązania dotyczą także specjalnie zaprojektowanych urządzeń służących do przechowywania i dozowania ODF, a także metod znakowania i identyfikacji pojedynczych dawek leku. W pracy przedstawiono przegląd piśmiennictwa z ostatnich lat, dotyczący nowych rozwiązań technologicznych w zakresie sporządzania filmów ulegających rozpadowi w jamie ustnej z uwzględnieniem metod wytwarzania, modyfikacji uwalniania substancji leczniczej oraz możliwości ich zastosowania w indywidualizacji terapii.One of the mains factors affecting the effectiveness and safety of the therapy is the development of an appropriate dosage form adapted to the age of the patients and ease to administer as well as a dosing devices that provide flexible dosing. This approach is in accordance with the idea of patient-centered treatment. Given advantages such as safety, easy swallowing and flexible dose adjustment, special attention is paid to oral dosage forms such as orally disintegrating tablets, minitablets and orodispersible films (ODF). The ODF films are indicated as a suitable dosage form for pediatric, geriatric and uncooperative patients due to their fast disintegration in the mouth without need for water to facilitate swallowing, adhesion to the oral cavity to prevent spitting out the medicine and the ability to adjust the dose of the drug for an individual patient. According to many studies, orodispersible films are well accepted by infants and preschool children, their caregivers (nurses) and parents. They have the form of a postage stamp sized strip of thin polymeric film applied on the tongue. The ODF films can be manufactured using various methods, i.e. casting method, hot melt extrusion, electrospinning or printing (inkjet, flexographic and 3D printing) on an industrial scale and potentially in hospital pharmacies. Extemporaneous preparation of the ODF films create more dose flexibility affecting patient’s adherence to pharmacotherapy. Innovative solutions in this area concern also designed specifically devices for storage and dosing of ODF, as well as methods of labeling and identification of single doses, for example Quick Response (QR) codes. The paper presents a review of the literature from recent years regarding new technology in the terms of the ODF films preparation, including manufacturing methods and modification of the drug release, as well as the possibilities of their application in individualization of the therapy especially in pediatric and geriatric population

Practical aspects of using Witepsol H15 in pharmaceutical compounding

New excipients increase new possibilities of the modifications in the composition of a compounded drugs. One of the examples is a Witepsol H15 suppository base registered in 2018 as an alternative to the previously used cocoa oil. The use of Witepsol H15 requires the determination of the replacement factors for active substances and excipients to calculate the optimal amount of this suppository base to prepare a certain number of suppositories. The classical method, which has been used so far, is based on the measurements of the mass of the suppositories with and without API, and the determination of the replacement factor using a calculation formula. Taking into account the differences between replacement coefficients resulting for example from a type and concentration of the active substance or excipient, the method of mixing and its parameters, it is reasonable to introduce an alternative calculation method based on the density measurements determined pycnometrically. Density measurements of excipients, APIs and selected medicinal products were carried out using the helium pycnometry method. Based on the ratio between density of the substrate to the API/excipient, the replacement coefficients were calculated. In total, two suppository bases (Witepsol H15 and Cacao oleum), 17 active substances, 2 excipients and 8 medicinal products were tested. The results were presented in tables, compared with available literature data and percentage differences were calculated. In order to complete the practical information regarding use of Witepsol H15, the numerous test on the functional properties of the base were carried out, including: volume contraction, sensitivity to process factors, thermal changes during heating and cooling. The ability to reduce the volume of the base during solidification has been confirmed, which allows an easy withdrawal of the suppository from the mold before application. The average contraction for Witepsol H15 is 3.23%, which is about 3 times higher compared to cocoa oil (1.13%). An analysis of the behavior during cooling of Witepsol H15 heated to different temperatures, was carried out and it was found that the overheated base shows stepped thermal changes profile while solidifying. The profile of temperature changes of properly liquefied base is predictable and does not show dynamic changes. Based on the DSC data, the liquid fraction content of Witepsol H15 was calculated. The base heated previously to 45 °C contains more liquid components than the unheated base. A practical implication is the recommendation to not overheat the base in order to obtain proper liquefaction of the suppository mass, easy filling of molds and limitation in the sedimentation of ingredients in suppositories. The results of performed studies confirm the usefulness of helium pycnometry to measure the density of substances and suppository bases, and to determine on their basis the displacement coefficients of active substances/excipients not included in the compendia so far. The helium pycnometry method enables the calculation of the displacement coefficient in the objective manner, independent of many factors, such as: base variability, preparation method, mixing parameters, content of API and excipients, size and load of the mixing container, conditions of solidification of the suppository mass. The replacement factors obtained in this way may be helpful in compounding practice. With the correct selection of mixing parameters, they lead to the obtainment of optimal amount of liquefied suppository mass necessary to fill the molds

Compression-Induced Phase Transitions of Bicalutamide

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.Polish National Science Centre 2015/16/W/NZ7/0040

A Bulb of Narcissus on the Egyptian Mummy from University of Wrocław Collection

The object of the present study is the ancient bulb of the narcissus found on the mummy, probably of the Ptolemaic period, brought to Wrocław from Italy in the sixteenth century AD. For about four hundred years the mummy was kept by the successive owners of one of pharmacies in Wrocław, and after the World War II became the possession of Wrocław University. Computed tomography made in 2002 revealed an atypical object lying under the left hand of the mummy. Extracted in 2004 it appeared to be the bulb of a flower, and botanical analysis has revealed that it represents the Narcissus tazetta L. species. Although the narcissus was known in Egypt, its identification in the ancient sources has never been attempted. Thanks to the analysis of the bio-medical properties of the narcissus, compared with some descriptions of remedies proposed by the medical papyri Ebers and Hearts, as well as with some religious magical texts an identification of the sennut plant with narcissus is proposed here.The object of the present study is the ancient bulb of the narcissus found on the mummy, probably of the Ptolemaic period, brought to Wrocław from Italy in the sixteenth century AD. For about four hundred years the mummy was kept by the successive owners of one of pharmacies in Wrocław, and after the World War II became the possession of Wrocław University. Computed tomography made in 2002 revealed an atypical object lying under the left hand of the mummy. Extracted in 2004 it appeared to be the bulb of a fl ower, and botanical analysis has revealed that it represents the Narcissus tazetta L. species. Although the narcissus was known in Egypt, its identification in the ancient sources has never been attempted. Thanks to the analysis of the bio-medical properties of the narcissus, compared with some descriptions of remedies proposed by the medical papyri Ebers and Hearts, as well as with some religious magical texts an identification of the sennut plant with narcissus is proposed here