Lipid-based systems as promising approach for enhancing the bioavailability of poorly water-soluble drugs

Low oral bioavailability as a consequence of low water solubility of drugs is a growing challenge to the development of new pharmaceutical products. One of the most popular approaches of oral bioavailability and solubility enhancement is the utilization of lipid-based drug delivery systems. Their use in product development is growing due to the versatility of pharmaceutical lipid excipients and drug formulations, and their compatibility with liquid, semi-solid, and solid dosage forms. Lipid formulations, such as self-emulsifying (SEDDS), self-microemulsifying SMEDDS) and self-nanoemulsifying drug delivery systems (SNEDDS) were explored in many studies as an efficient approach for improving the bioavailability and dissolution rate of poorly water-soluble drugs. One of the greatest advantages of incorporating poorly soluble drugs into such formulations is their spontaneous emulsification and formation of an emulsion, microemulsion or nanoemusion in aqueous media. This review article focuses on the following topics. First, it presents a classification overview of lipid-based drug delivery systems and mechanisms involved in improving the solubility and bioavailability of poorly water-soluble drugs. Second, the article reviews components of lipid-based drug delivery systems for oral use with their characteristics. Third, it brings a detailed description of SEDDS, SMEDDS and SNEDDS, which are very often misused in literature, with special emphasis on the comparison between microemulsions and nanoemulsions

Investigation of design space for freeze-drying injectable ibuprofen using response surface methodology

This study explores the use of a statistical model to build a design space for freeze-drying two formulations with ibuprofen. A 2 × 3 factorial experimental design was used to evaluate independent variables (filling volume and annealing time) and responses as residual moisture content, specific surface area and reconstitution time. A statistical model and response surface plots were generated to define the interactions among the selected variables. The models constructed for both formulations suggest that 1 ml of filled volume and no annealing should be used to achieve optimal residual moisture content, specific surface area and reconstitution time. The proposed models were validated with additional experiments, in which the responses observed were mainly in close agreement with the predicted ones. Additionally, the established models demonstrate the reliability of the evaluation procedure in predicting the selected responses

Solubilization of ibuprofen for freeze dried parenteral dosage forms

Ibuprofen, a weakly acidic non-steroidal anti-inflammatory drug having poor aqueous solubility, is a challenging drug for the development of pharmaceutical formulations, resulting in numerous research attempts focusing on improvement of its solubility and consequently bioavailability. Most studies have been done for solid dosage forms, with very little attention paid to parenterals. Hence, the main purpose of the present study was to enhance ibuprofen solubility as a result of formulation composition and the freeze drying process. Moreover, the purpose was to prepare a freeze dried dosage form with improved ibuprofen solubility that could, after simple reconstitution with water for injection, result in an isotonic parenteral solution. Solubility of ibuprofen was modified by various excipients suitable for parenteral application. Drug interactions with selected excipients in the final product/lyophilisate were studied by a combined use of XRPD, DSC, Raman and ssNMR. Analyses of lyophilized samples showed solubility enhancement of ibuprofen and in situ formation of an ibuprofen salt with the alkaline excipients used

Subkutano apliciranje monoklonskih protiteles: pregled sestavin zdravil

Razvija se vse več bioloških zdravil, med katerimi prevladujejo zdravila z monoklonskimi protitelesi (angl. monoclonal antibodies, mAb), ki omogočajo specifično in učinkovito zdravljenje z manj neželenimi učinki. Zaradi kompleksne in občutljive proteinske zgradbe mAb je treba takšna zdravila vnašati parenteralno. Intravensko apliciranje, ki prevladuje, je lahko boleče, dolgotrajno in zahteva celo hospitalizacijo. Zato je vse več zdravil z mAb v razvoju namenjenih subkutani aplikaciji, ki je hitrejša, omogoča nižje stroške zdravljenja in boljše sodelovanje bolnikov. Subkutano pa lahko vbrizgamo le majhen volumen raztopine, zato so pogosto potrebne visoke koncentracije mAb, ki lahko povečajo viskoznost raztopin in povzročijo fizikalno nestabilnost molekul mAb v njih. Zdravila z mAb zato vsebujejo pufre, stabilizatorje in pomožne snovi za znižanje viskoznosti, ki prispevajo tudi k fizikalni stabilnosti mAb. Poleg teh sestavin članek predstavi tudi pomožne snovi, ki omogočajo vbrizgati večji volumen zdravila v podkožje in kombinacije terapevtskih mAb. Opisani so tudi inovativni sistemi za subkutano apliciranje mAb, kot so kompleksi, nanoklastri, suspenzije, mikrodelci in hidrogeli, ki so še v fazi razvijanja