Bożena Karolewicz

Ophthalmic Drug Dosage Forms: Characterisation and Research Methods

This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommended in vitro and in vivo studies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patients compliance.

A review of polymers as multifunctional excipients in drug dosage form technology

In the article, groups of multifunctional polymers used in drug dosage form technology were classified and evaluated. These compounds, in addition to their basic function as excipients, may have additional properties, e.g. stimuli sensitivity, enzyme inhibition, intestinal epithelium penetration enhancement, efflux pump inhibition, taste-masking, pharmacological activity and the ability to interact with enzymes responsible for drug metabolism. While classifying specific groups of multifunctional polymers, special emphasis was placed on the advantages of using them when designing new drug. Such advantages include, i.a., increasing substance bioavailability, improving substance stability during formulation and the possibility of obtaining forms of controlled or localized release to a specific site in the organism.

Thermal, spectroscopic and dissolution studies of lovastatin solid dispersions with acetylsalicylic acid

Lovastatin (LOV) is widely used for the treatment of hypercholesterolemia. The poor water solubility of LOV leads to its poor gastrointestinal absorption and results in poor bioavailability. In this study, a preparation of solid dispersions with acetylsalicylic acid (ASA) was studied to improve the dissolution rate of LOV. Solid dispersions were prepared using various mass ratios of both components through the grinding method. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction (XRPD) were used to characterize prepared solid dispersions. Their dissolution behaviors were also compared. LOV and ASA formed a simple eutectic phase diagram as indicated by DSC. The results obtained from FTIR spectroscopy and XRPD showed no evidence of drug–drug interaction. The dissolution studies indicated that the in vitro dissolution rate of LOV released from solid dispersions containing 10, 20, 40 and 60 mass% LOV was improved compared with the drug alone.

Thermal stability and decompositions kinetics under non-isothermal conditions of imatinib mesylate α form.

The thermal decomposition and kinetic parameters of synthetized imatinib mesylate α form α form were determined by thermogravimetry (TGA/DTG) under non-isothermal conditions. The experiments were performed at a 25-940°C temperature range at five different heating rates: 2.5Kmin(-1), 5Kmin(-1), 10Kmin(-1), 15Kmin(-1) and 20Kmin(-1) per minute in a nitrogen atmosphere. Imatinib mesylate α form presents one-step mass loss during the degradation process. The thermal stability of the examined material, the melting temperature (Tonset=220.6°C) and ΔH fusion=-95.74Jg(-1) at a heating rate of 10°Cmin(-1) was established. The values of activation energies have been estimated using Kissinger, Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) methods.

Physicochemical characterization and dissolution studies of acyclovir solid dispersions with Pluronic F127 prepared by the kneading method.

Abstract The dissolution rate of anhydrous acyclovir was improved by the preparation of physical mixtures and solid dispersions with the non-ionic polymer Pluronic F127 using the kneading method at different drug-to-polymer ratios. The obtained physical mixtures and solid dispersions were examined in terms of drug content and possible physical and chemical interactions between the drug and polymer using FTIR spectral studies, differential scanning calorimetry and powder X-ray diffraction analysis. The dissolution rate of acyclovir was determined using the rotating disk method. It was found that the minimal content of the polymer within the mixtures needed to increase the dissolution rate of the drug was 50 %.

Development of the rectal dosage form with silver-coated glass beads for local-action applications in lower sections of the gastrointestinal tract

Abstract Context: Recent findings indicating the anti-inflammatory action of silver preparations through modulation of the gut microbiota and apoptosis of inflammatory cells predestine silver use in inflammatory bowel disease (IBD). Objective: The aim of our study was to validate the possibility of effective silver release from silver-coated glass beads for anti-inflammatory local application in the lower sections of the gastrointestinal (GI) tract. Materials and methods: Silver-coated glass beads were prepared using magnetron method. Release of silver from the silver-coated glass bead surface was carried out in BIO-DIS reciprocating cylinder apparatus. Erosion of silver coating and indirect estimation of the silver release dynamics was assessed using scanning electron microscope. Rectal suppositories containing silver-coated glass beads were prepared using five different methods (M1–M5) and X-ray scanned for their composition. Results and discussion: The XR microanalysis and the chemical composition analysis evidenced for a rapid (within 30 min) release of nearly 50% of silver from the coating of the glass beads, which remained stable up to 24 h of incubation. The most homogeneous distribution of beads in the entire volume of the suppository was obtained for formulation M5, where the molten base was poured into mold placed in an ice bath, and the beads were added after 10 s. Conclusions: Our study is the first to present the concept of enclosing silver-coated glass beads in the lipophilic suppository base to attenuate inflammation in the lower GI tract and promises efficient treatment with reduced side effects.

The role of the polymer matrix in solvent-free hot melt extrusion continuous process for mechanochemical synthesis of pharmaceutical cocrystal

Graphical abstract Figure. No caption available. ABSTRACT Solid‐state synthesis of pharmaceutical cocrystals is of contemporary interest as it offers an efficient way to modify the physicochemical properties of Active Pharmaceutical Ingredient (API) including its melting point, solubility, compressibility or physical stability, without compromising its structural integrity and bioactivity. Therefore, research of novel and emerging techniques for solvent‐free, continuous and scalable methods for cocrystal formation is of paramount importance for further industrial development. In this work we form a basis for knowledge‐based synthesis and formulation of model pharmaceutical cocrystal (flufenamic acid, FFA: nicotinamide, NA; 1:1) via matrix‐assisted cocrystallisation (MAC) using Hot Melt Extrusion (HME). Five different polymers frequently used in pharmaceutical drug delivery: Poloxamer P407 (PXM), PEG‐PVA copolymer, Soluplus® (SOL), PVPVA64 and HPMCAS with different structural features and physicochemical properties were investigated as functional matrices for FFA:NA cocrystal synthesis via HME. Significant decrease of the torque value during MAC process was observed for all investigated polymers as compared to extrusion of neat FFA:NA cocrystal. The FFA:NA cocrystal encapsulated in the polymer matrix was successfully formed using semicrystalline PXM and PEG‐PVA polymers at all investigated FFA:NA/polymer ratios. The use of amorphous polymers (SOL, PVPVA64, HPMCAS) as a cocrystallisation matrix resulted in formation of FFA:NA cocrystal embedded in an amorphous FFA:NA/polymer matrix (at polymer contents of 10 and 20 wt.%) or FFA:NA/polymer amorphous composites at SOL and PVPVA64 content of 30 wt.%. Furthermore, the significant increase of FFA dissolution was observed for FFA:NA cocrystal encapsulated in PXM and PEG‐PVA matrices as compared to neat FFA form I. FFA form III and FFA:NA cocrystal. The presented work enables for the first time knowledge‐based approach for simultaneous synthesis and formulation of pharmaceutical cocrystals via Hot Melt Extrusion a solvent‐free, scalable and continuous process.

THE INFLUENCE OF A DENTAL FORMULATION PREPARED WITH CHITOSAN ON THE PHARMACEUTICAL AVAILABILITY OF CLOTRIMAZOLE

The present work involves the development of a dental gel composition obtained on the basis of clotrimazole incorporated into chitosan in order to improve drug solubility. Solid dispersions were prepared by using two methods: grinding and kneading. The solid dispersion varied the ratio of chitosan to drug to increase the volume of the drug; the ratios were 5:5, 3:7, 2:8, 1:9. The mixtures were subjected to the dissolution rate of clotrimazole. The presence of chitosan improved the drug solubility; a better solubility from the solid dispersion prepared by the grinding method was obtained from the ratio of drug to polymer of 1+9. The rate of dissolution of clotrimazole was improved 17 times compared to the pure drug. Fourier transform infrared spectroscopy (both infrared and X-ray diffraction) revealed no new chemical structure of the tested connections and concluded that there was no interaction between the drug and the polymer in the test diffractions. Solid dispersions with the best parameters were used to prepare hydrogels, and the pharmaceutical availability of clotrimazole was analysed. The best properties were characterized by a hydrogel that was composed of the ratio of the amount of drug to polymer 5:5. The study demonstrated the availability of a pharmaceutical drug release at a therapeutic concentration in the first hour of the study. The use of the appropriate balance between clotrimazole and chitosan and the development of the hydrogel composition may affect the improvement of the drug solubility and may create the possibility of obtaining sustained or controlled release of the drug substance. .

THE INFLUENCE OF SELECTED POLYMERS ON THE RHEOLOGICAL PROPERTIES OF HYDROGELS WITH CHITOSAN APPLIED ON THE SKIN

The aim of the study was to evaluate the effect of methylcellulose and carboxymethylcellulose on the rheological properties of hydrogels applied to skin on chitosan in the presence of the additives propylene glycol and glycerol. Rheological studies showed that the tested gels are non-newtonian systems, and have thixotropic properties. Substrates made of methylcellulose and chitosan are characterised by higher shear values than those obtained with carboxymethylcellulose. The addition of polymers had a positive influence on the dispersion of hydrogels, and the addition of excipients increased firmness, consistency and cohesiveness of the gels. Larger increases were observed with the addition of 10% of glycol propylene and glycerol contents for methylcellulose and of 20% of carboxymethylcellulose.