Aleksandra Amelian

Development and Evaluation of Liquid and Solid Self-Emulsifying Drug Delivery Systems for Atorvastatin

The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS) for poorly soluble atorvastatin. To optimize the composition of liquid atorvastatin-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability, droplet size and zeta potential analysis) were performed. Due to the disadvantages of liquid SEDDS (few choices for dosage forms, low stability and portability during the manufacturing process), attempts were also made to obtain solid SEDDS. Solid SEDDS were successfully obtained using the spray drying technique from two optimized liquid formulations, CF3 and OF2. Despite liquid SEDDS formulation, CF3 was characterized by lower turbidity, higher percentage transmittance and better self-emulsifying properties, and based on the in vitro dissolution study it can be concluded that better solubilization properties were exhibited by solid formulation OF2. Overall, the studies demonstrated the possibility of formulating liquid and solid SEEDS as promising carriers of atorvastatin. SEDDS, with their unique solubilization properties, provide the opportunity to deliver lipophilic drugs to the gastrointestinal tract in a solubilized state, avoiding dissolution—a restricting factor in absorption rate of BCS Class 2 drugs, including atorvastatin.

Application of standard cell cultures and 3D in vitro tissue models as an effective tool in drug design and development

Cell culture systems are essential tools used in a wide range of biomedical and clinical studies. Two dimensional cell culture models (2D) provide basic information on cytotoxicity, penetration and accumulation of drugs in cells and they are of outmost importance when selecting new compounds of the desired biopharmaceutical properties as candidates for novel drugs. The improvement over 2D growing cells are three dimensional (3D) tissue models that mimic in vivo conditions and the functions of living tissue more accurately. These models reduce the cost of drug development, enable more efficient drug screening, minimise failure rate in medicine discovery and eliminate animal use during experiments. The article provides an overview of 2D cell cultures and 3D tissue models - their properties, basic procedures, conditions of culturing and applications.

Alginate microspheres obtained by the spray drying technique as mucoadhesive carriers of ranitidine

Abstract The present study is aimed at formulation of alginate (ALG) microspheres with ranitidine (RNT) by the spray drying method. Obtained microspheres were characterized for particle size, surface morphology, entrapment efficiency, drug loading, in vitro drug release and zeta potential. Mucoadhesive properties were examined by a texture analyser and three types of adhesive layers - gelatine discs, mucin gel and porcine stomach mucosa. Microspheres showed a smooth surface with narrow particle size distribution and RNT loading of up to 70.9 %. All formulations possessed mucoadhesive properties and exhibited prolonged drug release according to the first-order kinetics. DSC reports showed that there was no interaction between RNT and ALG. Designed microspheres can be considered potential carriers of ranitidine with prolonged residence time in the stomach

Characterization and taste masking evaluation of microparticles with cetirizine dihydrochloride and methacrylate-based copolymer obtained by spray drying

Abstract Taste of a pharmaceutical formulation is an important parameter for the effectiveness of pharmacotherapy. Cetirizine dihydrochloride (CET) is a second-generation antihistamine that is commonly administered in allergy treatment. CET is characterized by extremely bitter taste and it is a great challenge to successfully mask its taste; therefore the goal of this work was to formulate and characterize the microparticles obtained by the spray drying method with CET and poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate 1:2:1 copolymer (Eudragit E PO) as a barrier coating. Assessment of taste masking by the electronic tongue has revealed that designed formulations created an effective taste masking barrier. Taste masking effect was also confirmed by the in vivo model and the in vitro release profile of CET. Obtained data have shown that microparticles with a drug/polymer ratio (0.5:1) are promising CET carriers with efficient taste masking potential and might be further used in designing orodispersible dosage forms with CET.

Taste-masking assessment of orally disintegrating tablets and lyophilisates with cetirizine dihydrochloride microparticles

Orally disintegrating tablets and oral lyophilisates are novel attractive dosage forms that disintegrate or dissolve in the buccal cavity within seconds without necessity of drinking. The major limitation in designing of these dosage forms is unpleasant taste of the drug substance. Cetirizine dihydrochloride is a H1-antihistamine substance indicated for the treatment of allergy. It is characterized by extremely bitter taste, therefore in order to deliver cetirizine dihydrochloride using orodispersible formulations, effective taste-masking is required. The aim of this study was to investigate whether microparticles containing cetirizine dihydrochloride could be successfully used to formulate orally disintegrating tablets by direct compression method and oral lyophilisates by freeze-drying process. Taste masking of cetirizine dihydrochloride was achieved by the spray-drying technique using Eudragit® E PO as the drug agent carrier. Based on the preliminary studies, optimal compositions of microparticles, tablets and lyophilisates were chosen. Obtained dosage forms were characterized for drug content, disintegration time and mechanical properties. In order to determine whether the microparticles subjected to direct compression and freeze-drying process effectively mask the bitter taste of cetirizine dihydrochloride, the in vivo and in vitro evaluation was performed. The results showed that designed formulates with microparticles containing cetirizine dihydrochloride were characterized by appropriate mechanical properties, uniformity of weight and thickness, short disintegration time, and the uniform content of the drug substance. Taste-masking assessment performed by three independent methods (e-tongue evaluation, human test panel and the in vitro drug release) revealed that microparticles with Eudragit® E PO are effective taste – masking carriers of cetirizine dihydrochloride and might be used to formulate orally disintegrating tablets and oral lyophilisates.

Evaluation of lyophilisates with taste-masking microshperes by electronic tongue

Novel drug delivery systems, which facilitate swallowing and improve patient adherence due to bitter taste masking of Active Pharmaceutical Ingredient (API), gain an increasing interest in recent years. Usually, studies on the taste of pharmaceutical products are conducted by human taste panel, but it concerns ethical doubts. Electronic tongue is one of the candidate tools allowing for fast, repeatable, and objective analysis of pharmaceuticals. In this work a sensor array composed of cross-selective electrodes was coupled with Principal Component Analysis in order to assess the taste-masking efficiency of the microencapsulated API (cetirizine dihydrohloride) formulated in lyophilisates. The obtained results show that presented electronic tongue can be used for the recognition of the studied pharmaceutical formulations and evaluation of the taste-masking effect.