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Context: Although several methods have been investigated to measure the film thickness of tablets and its correlation with the dissolution behavior, much fewer such investigations exist for pharmaceutical pellets. Objective: To study the possibility of measuring the film thickness and predicting the dissolution behavior of pellets produced in different fluid bed equipments with Raman spectroscopy. Materials and methods: Pyridoxine hydrochloride-layered pellets were produced and coated in two different Strea-1 equipments. Raman spectra were collected and analysed to set up a calibration model based on the film thickness data calculated from Camsizer analysis results. Dissolution tests were done according to Ph. Eur. standards. Results: Raman spectroscopy proved to be a good tool in the measurement of film thickness. Polymer weight gain showed a linear correlation with film thickness but was a poor predictor of dissolution results below a threshold value. Conclusion: The Raman spectroscopic measurement of a small sample can provide accurate data of the film thickness. The investigation suggests that a threshold value might exist for the film thickness above which it can be used to judge future dissolution results. [ABSTRACT FROM AUTHOR]

The aim of our research was to investigate the effect of the length of the polymer chain and the concentration of triethyl citrate used as a plasticizer on the thermal stability of the film structure in the case of two ethyl cellulose films (EC 10 and EC 45) used for preparing MR dosage forms. The influence of storage time was studied by monitoring the changes in the thermoanalytical parameters and by performing TG-MS examinations. It was found that the decomposition of the plasticizer from the arising film structure is retarded and a more homogeneous sample, therefore a better film can be prepared from EC 45. Mass spectrography performed as a coupled technique also proved that the films stayed stable until approximately 200 °C. Based on the above results, the composition prepared from EC 45 polymer with 5% triethyl citrate as plasticizer is recommended for making MR dosage forms. [ABSTRACT FROM AUTHOR]

Introduction: The focus of this work was to produce matrix pellets made by extrusion/ spheronization using two types of equipment. The aim was to accomplish the laboratory-scale I process that has been already optimized and accepted with another type of equipment (laboratory-scale II). Methods: A matrix pellet formulation consisting of MCC, Eudragit NE 30D and diclofenac sodium was used in the two types of equipment. Physico-chemical parameters and the dissolution profiles of the pellets in phosphate buffer pH 6.8 were compared. Results: Pellets from both processes were similar in shape and tensile strength. They differed in particle size and dissolution profile. This may be contributed to different spheronization conditions. [ABSTRACT FROM AUTHOR]

The physicochemical properties of polymers planned to be applied as mucoadhesive films were studied. Two types of Klucel® hydroxypropylcellulose (LF and MF) were used as film-forming polymers. Hydroxypropylcellulose was incorporated in 2w/w% with glycerol and xylitol as excipients and lidocaine base as an active ingredient at 5, 10 or 15w/w% of the mass of the film-forming polymer. The free volume changes of the films were investigated by positron annihilation lifetime spectroscopy, the mechanical properties of the samples were measured with a tensile strength tester and contact angles were determined to assess the surface properties of the films. It was found that the Klucel® MF films had better physicochemical properties than those of the LF films. Klucel® MF as a film-forming polymer with lidocaine base and both excipients at 5w/w% exhibited physicochemical properties and good workability. The excipients proved to exert strong effects on the physicochemical properties of the tested systems and it is very important to study them intensively in preformulation studies in the pharmaceutical technology in order to utilise their benefits and to avoid any disadvantageous effects. [ABSTRACT FROM AUTHOR]

The preparation of pellets using a high-shear granulator in a rapid single-step is considered a good economic alternative to the extrusion spheronization process. As process parameters and material attributes greatly affect pellet qualities, successful process optimization plays a vital role in producing pellet dosage forms with the required critical quality attributes. This study was aimed at the development and optimization of the pelletization technique with the Pro-CepT granulator. According to the quality by design (QbD) and screening design results, chopper speed, the volume of the granulating liquid, binder amount, and impeller speed were selected as the highest risk variables for a two-level full factorial design and central composite design, which were applied to the formula of microcrystalline cellulose, mannitol, and with a binding aqueous polyvinylpyrrolidone solution. The design space was estimated based on physical response results, including the total yield of the required size, hardness, and aspect ratio. The optimized point was tested with two different types of active ingredients. Amlodipine and hydrochlorothiazide were selected as model drugs and were loaded into an optimized formulation. The kinetics of the release of the active agent was examined and found that the results show a correlation with the electrokinetic potential because amlodipine besylate can be adsorbed on the surface of the MCC, while hydrochlorothiazide less so; therefore, in this case, the release of the active agent increases. The research results revealed no significant differences between plain and model drug pellets, except for hydrochlorothiazide yield percent, in addition to acceptable content uniformity and dissolution enhancement.

Hydrophobic ion pairing (HIP) complexation was found to be an efficient approach in modulating the release and enhancing the stability and encapsulation of hydrophilic macromolecules such as proteins in hydrophobic nano/microcarriers. The present work strives to develop and optimize the preparation of the HIP complex of the antimicrobial enzyme lysozyme (LYZ) with the ion-pairing agent (IPA) sodium dodecyl sulphate (SDS) relying on the quality-by-design (QbD) approach. The quality target product profile (QTPP) includes the achievement of maximal lipophilicity in a reversible manner to enable the maintenance of biological activity. The related critical quality attributes (CQAs) were defined as complexation efficacy, complex stability, enzyme recovery and activity. Three risk assessment (RA) tools were used to identify and rank the critical process parameters (CPPs) and critical material attributes (CMAs). From this assessment, the pH of the medium, LYZ:SDS molar ratio and drying conditions were determined as high-risk factors that need to be investigated. To the best of our knowledge, for the first time, electrostatic titration was used as a smart approach to determine the optimum molar ratio at different pH values. Based on the predefined CQAs, pH 8 with an LYZ/SDS molar ratio of 1:8 was found to be the optimal condition for complexation efficiency and recovery (%) of a biologically active enzyme. A cost-effective drying process based on a ventilated oven was developed, which resulted in complex qualities comparable to those obtained by the commonly used freeze-drying method. In a nutshell, the optimum conditions for the preparation of the LYZ/SDS HIP complex were efficiently facilitated by the rational application of QbD principles and the utilization of efficient electrostatic titration and ventilated oven-drying methods., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Buccal drug administration is a less explored area, therefore researchers and companies focus on its research because of its innovative potential and opportunities. Buccal polymer films (patches) are considered to be an innovative form and have a great number of advantageous properties. Firstly, patients who suffer from swallowing problems and children can also apply them. The active pharmaceutical ingredient enters the systemic circulation directly without degradation and transformation. The aim of this study was to formulate buccal films with sodium alginate (SA) because it is a rarely used, innovative polymer for the formulation of buccal films. The mechanical, chemical properties and dosage forms of the prepared films were investigated with different methods. To formulate the films, cetirizine dihydrochloride (CTZ) was used as model drug, and glycerol (GLY) was added to make the films more elastic. The samples were prepared and stored at room temperature. As a result, it can be seen that the mechanical properties of all film compositions show good results, especially breaking hardness. The films with high SA concentration containing CTZ had appropriate mucoadhesion forces, so these samples are suitable for application on the buccal mucosa. The results of dissolution confirmed this finding. Finally, it can be said we formulated fast dissolving films and it can be concluded that the films prepared with 3% SA concentration containing 1% and 3% GLY can be recommended for buccal application., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Counterfeiting of the products for healing is as old as trading, and it is difficult to quantify the magnitude of the problem. It is known that substandard and/or falsified (SF) medicines are a growing global threat to health, and they cause serious social and economic damage. The EU has a strong legal framework for medicines, it is mandatory to meet the requirements of Directive 2011/62/EU. Serialisation prevents SF medicinal products from entering the legal distribution chain. The present study is an extension of the original idea and aims to develop a laser technology-based method to mark an individual traceable code on the surface of the tablet, which technology can also be used for marking personalized medicines. The method is based on the ablation of the upper layer of a double-layer, differently coloured coating. The 2D code should be formed without harming the functional layer, and anyone with a smartphone integrated with a camera should be able to authenticate these drugs with a suitable application. The present findings confirmed that KrF excimer laser and Ti:sapphire femtosecond laser are efficient and reliable for marking. These should be promising candidates for pharmaceutical companies that would like to have additional protection against drug counterfeiters., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

As proven in clinical trials, superficial fungal infections can be effectively treated by single topical application of terbinafine hydrochloride (Ter-HCl) in a film forming system (FFS). Poly(lactic-co-glycolic acid) (PLGA) derivatives, originally synthesized with intention to get carriers with optimized properties for drug delivery, and multifunctional plasticizers - ethyl pyruvate, methyl salicylate, or triacetin - were used for formulation of Ter-HCl loaded FFSs. After spraying, a biodegradable, transparent, adhesive, and occlusive thin layer is formed on the skin, representing drug depot. In situ formed films were characterized by thermal, structural, viscoelastic, and antifungal properties as well as drug release and skin penetration. DSC and SEM showed fully amorphous films with Ter-HCl dissolved in PLGA in high concentration (up to 15%). FFSs are viscoelastic fluids with viscosity which can be easily adjusted by the type of plasticizer used and its concentration. The formulations showed excellent bioadhesion properties, thus ensuring persistence on the skin. In situ film based on branched PLGA/A plasticized with 10% of ethyl pyruvate allowed prolonged release of Ter-HCl by linear kinetics for the first 6 days with a total time of almost 14 days. During ex vivo human skin penetration experiment, Ter-HCl was found to be located only in its target layer, the epidermis. According to our results, plasticized branched PLGA derivatives loaded by Ter-HCl are suitable for the development of FFSs for superficial fungal infections treatment., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: The main objective of present review is to explore and evaluate the effectiveness of recently developed methods to improve the bioavailability of orally administered biopharmaceutical drugs., Methods: A systematic search of sciencedirect, tandfonline and Google Scholar databases based on various sets of keywords was performed. All results were evaluated based on their abstracts, and irrelevant studies were neglected during further evaluation., Results: At present, biopharmaceuticals are used as injectable therapies as they are not absorbed adequately from the different routes of drug administration, particularly the oral one. Their insufficient absorption is attributed to their high molecular weight, degradation by proteolytic enzymes, high hydrophilicity and rigidity of the absorptive tissues. From industrial aspect incorporation of enzyme inhibitors (EIs) and permeation enhancers (PEs) and mucoadhesive polymers into conventional dosage forms may be the easiest way of formulation of orally administered macromolecular drugs, but the effectiveness of protection and absorption enhancement here is the most questionable. Conjugation may be problematic from regulatory aspect. Encapsulation into lipid-based vesicles sufficiently protects the incorporated macromolecule and improves intestinal uptake but have considerable stability issues. In contrast, polymeric nanocarriers may provide good stability but provides lower internalization efficacy in comparison with the lipid-based carriers., Conclusion: It can be concluded that the combination of the advantages of mucoadhesive polymeric and lid-based carriers in hybrid lipid/polymer nanoparticles may result in improved absorption and might represent a potential means for the oral administration of therapeutic proteins in the near future. Graphical abstract Delivery systems for oral protein daministration.

The demand for revealing the medical advantages offered by nanotechnology is increasing more and more. Titanate nanotubes deserve consideration in many aspects. Their production is easy, cost-effective and environmentally friendly. Due to their special physico-chemical properties, titanate nanotubes can play an important role in different fields of therapy, such as medical diagnostics, implantology, or even as cancer treatment. The aim of our work is to present the titanate nanotubes and give an overview on their medical applicability through the results of previous researches.

With the increasing number of protein active agents produced by the biotechnological route, the suitable analytical methods will also be important. The detection of small changes of protein and the monitoring of the processes of the biotechnological procedure are important. Biosensors can be applied for the detection of very low concentrations with nearly 100% selectivity. The aims of our work are to give basic information about biosensors, about their grouping and potential field of application.

Chloroquine-phosphate was suspended in various lipophilic and hydrophilic suppository bases in an amount of 250 mg/2.0 g. The authors studied the solidity and the disintegration time of the suppositories as well as the in vitro drug liberation with a membrane diffusion method. The effect of the storage time and the storage circumstances on the stability of the suppositories was observed. Tropics-resistance studies were also carried out at a temperature of 45 degrees C and at a relative humidity content of 75%, thus these suppositories may be used for the treatment of malaria. The Witepsol H 15 base was found to be the best in all respect for use in countries with a continental climate. Finally a function relationship was found between the concentration of the pharmacon and the diffusion time with linear regression analysis.