Search

Matrix tablets are the most popular method of oral drug administration, and polymeric materials have been used broadly in matrix formulations to modify and modulate drug release rate. The main goal of the system is to extend drug release profiles to maintain a constant in vivo plasma drug concentration and a consistent pharmacological effect. Polymeric matrix tablets offer a great potential as oral controlled drug delivery systems. Cellulose derivatives, like hydroxypropyl methylcellulose (HPMC) are often used as matrix formers. However, also other types of polymers can be used for this purpose including: Kollidon SR, acrylic acid polymers such as Eudragits and Carbopols. Nevertheless, polymers of natural origin like: carragens, chitosan and alginates widely used in the food and cosmetics industry are now coming to the fore of pharmaceutical research and are used in matrix tablets technology. Modern polymers allow to obtain matrix tablets by 3D printing, which enables to develop new formulation types. In this paper, the polymers used in matrix tablets technology and examples of their applications were described.

Microspheres and implants are injectable drug forms, which by special design and selection of appropriate excipients, provide for a long time constant release rate of an active substance in the body. Development of both would not be possible without advances in polymer technology and invention of safe and biocompatible polymers such as: polyesters, vinyl acetate derivatives or silicones. Polymeric matrices provide retardation of drug release--for some implants up to a few years. In addition, this paper presents examples of all commercially available medicinal products containing microspheres and implants, currently registered in Poland, together with their characteristics: composition, time course and frequency of administration. Comments are also enclosed on frequently occurring inconsistent terminology in pharmaceutical forms.

The article presents description of the most important parenteral forms, which release an active substance in sustained manner. Technological and biopharmaceutical information is supplemented with examples of commercial products, currently registered in Poland. Mechanism of drug release from the dosage form and duration of the process, role of other excipients and characteristics of certain medicinal products is presented. The information about suspensions and oily solutions for injection is summarized. Owing to specific chemical modifications and selection of suitable excipients, it was possible to develop these types of medicinal products for some antibiotics, hormones, antipsychotics and cytostatics. These formulations, after subcutaneous or intramuscular injection, release the active substances even for several weeks allowing to reduce the frequency of drug administration and finally help to improve patient's compliance. Here also the modified time course of insulin products achieved by selection of appropriate suspension form or insulin analogue is discussed.

Aim of the Study: Diclofenac and its sodium salt is one of the best-known and popular therapeutic agents from the group of NSAIDs used in medicine in many various pharmaceutical forms. Therapeutic products containing diclofenac sodium salt in doses of 100 mg and 75 mg with a qualitatively and quantitatively diversified share of excipients and a variable dosage form of the drug (solid capsules, tablets with modified release) were subjected to technological and pharmaceutical analysis. The effect of solid formulation components of polymer character making the core and the coating of the pharmaceutical form of therapeutic products on the disintegration time and pharmaceutical availability in pharmacopoeial receptor fluids was estimated., Materials and Methods: Market therapeutic products with diclofenac sodium in doses of 75 mg and 100 mg, technological analysis of the drug dosage form was conducted, disintegration time of solid oral dosage forms of the drug with diclofenac sodium salt was examined and research on pharmaceutical availability of diclofenac sodium salt from tested therapeutic products was conducted using the acid phase and the buffer phase according to the FP standards for delayed release enteral dosage forms. The experimental data was supplemented with the statistical analysis., Results: There are three formulations in the form of solid capsules and one formulation in the form of a coated tablet. All therapeutic products bear features of a dosage form of modified release of diclofenac sodium salt, frequently of a delayed release formula in the duodenum or the small intestine with regard to the limitation of typical undesirable effects after taking NSAIDs. Considerable diversity between solid capsules and the tablet with modified release during disintegration or hydration and swelling has been observed. In the environment of a receptor fluid--purified water (pH = 7) the capsule Dicloberl retard disintegrates at the fastest rate in 5,49 minutes, and then in the order: DicloDuo 75 mg--8,13 minutes and Olfen 100 SR--11,27 minutes. The hydration degree of gelatin walls of capsules depends on the pH of the receptor fluid. The availability of diclofenac sodium salt in given receptor fluids confirms the fact of significant connection of clinical effectiveness of the tested pharmaceutical forms with the activity of hydrogen ions (pH) of the environment in which there are therapeutic products, and excipients used for making the pharmaceutical phase., Conclusions: Tested therapeutic products with diclofenac sodium salt are differentiated by the type of a dosage form. Dicloberl retard contains the minimally indispensable number of simple, commonly used excipients. The research on the disintegration time may only be related to the products Dicloberl retard, Olfen 100 SR and DicloDuo 75 mg treating it as the time of deformation and disintegration of a capsule. In all three types of receptor fluids, the capsule Dicloberl retard has the fastest disintegration rate. The "acid phase" demonstrated stability of the products with a slight dissolution of diclofenac sodium salt on the level 1,3-4,18% of the Q release coefficient. In the environment of artificial intestinal juice, Dicloberl retard is more effective releasing larger amounts of diclofenac sodium salt during 4 hours of exposition (differences from 10% to 14% of the Q release coefficient).

Aim of Study: Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release., Materials and Methods: Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients., Results: The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration-dissolving of a tablet, is conducive to the reduction of gastrointestinal side effects and better tolerance of the therapeutic product by a patient. The study on pharmaceutical availability indicated relevant kinetic differences between tested therapeutic products. They are particularly visible between standard formulations and the one with prolonged release (Glucophage XR500). Its release profile bears features of kinetics similar to zero-order reactions., Conclusions: Tested therapeutic products contain a large amount of the biologically active substance in relation to the content of excipients. A higher content of excipients in a single tablet mass distinguishes Siofor in comparison with Glucophage i Metformax. The excipients used in the formulations of tested preparations are comparable. A higher percentage of binding agents (HPMC, PVP) is observed, but there is a lack of typical disintegrants which results in a longer disintegration time up to 15 minutes. Siofor disintegrates at the same time as Formetic, but longer than Glucophage i Metformax. Considering the large content of the active substance and pharmacological properties of metformin hydrochloride, such a disintegration might have beneficial consequences, because the amount of the free active substance in the gastrointestinal tract will increase over the longer time period what will reduce the level of gastrointestinal side effects. The release profiles of metformin hydrochloride from tested therapeutic products are comparable. The Glucophage XR 500 formulation with the release kinetics of metformin hydrochloride similar to the zero-order kinetics is completely different from the others. The above is confirmed by the mathematical analysis of release profiles of metformin hydrochloride from tested preparations where equations of lines describing the release profile are characterized by similar values of correlation coefficients.

Pre-formulation research was conducted on the application of Ex. Echinaceae aq. siccum in the production of a quickly disintegrating suspension tablet, a lozenge with kariostatic sugar alcohols (mannitol, sorbitol), and, above all, a solid drug form with controlled release of therapeutic agents included in the extract. Morphological parameters of tablets obtained in the course of experiment were estimated and the profiles of the release (diffusion) ofhydrophilic therapeutic agents into model receptor fluids with varying values of osmolarity (0.1 mol HCl approximately 200 mOsm/l, hypotonic hydrating fluid approximately 143 mOsm/l, and compensatory paediatric fluid approximately 272 mOsm/l) were examined. The study focused on the technological problem of determining the effect of hydrogel Carbopol structure on the ordering of diffusion ofhydrophilic therapeutic agents from a model drug form (a tablet) into model fluids with variable osmolarity.

The aim of the work was the evaluation of the conductivity changes in aqueous environment, consisting of chlorhexidine, and N-isopropylacrylamide derivative microgel, during increasing the temperature between 25 degrees C and 42 degrees C, as a prerequisite to develop the this microgel for controlled release of chlorhexidine, when alterations in temperature are involved. Conductivity of studied systems underwent specific alterations, when temperature increased. For the system with polymer PNM I the values of conductivity were in the range 104,47 microS/cm - 134,70 microS/ cm, for temperature range 25 degrees C and 42 degrees C. In the case of PNM II - CX system, respective values reached 91,75 microS/cm - 135,95 microS/cm. The lowest conductivity values were observed when PNM III - CX mixture was studied: 96,90 microS/cm and 117,37 microS/cm. When a complex of derivatives of N-isopropylacrylamide with chlorhexidine undergoes thermal alteration, there is a potential to obtain controlled release of chlorhexidine from the polymeric bead in the range between 25 degrees C and 42 degrees C. The affinity of chlorhexidine to the polymer may be assessed in this systems applying the conductivity measurements. The solubility of chlorhexidine in the polymeric systems should be in future evaluated, to determine role of this factor in the conductivity alterations.

The study is a continuation of research on manufacturing oral solid drug form containing extract from Epilobium parviflorum Schreb. This study aims at investigating the usefulness of selected high-molecular substances with particular consideration of chitosan (Ch), silicified microcrystalline cellulose (Prosolv) and croscarmellose sodium (Vivasol) as a carrier of E. parviflorum Schreb. extract in oral solid drug form in the process of direct tableting. In one series the alternative technological process (with initial granulation) was applied. The polymer carriers of extract were selected so as to obtain shorter disintegration time in relation to the earlier published studies and stability after longer time of storage. The effect of chitosan was estimated on selected morphological parameters of practical relevance during storage. The obtained results allow to state that the applied high-molecular adjuvant substances proved to be useful in adequate proportions in the production of tablets from dry extract from Epilobium parviflorum Schreb. through direct pressing of the tablet mass. The tablet properties in all series were in accordance with obligatory standards also after longer time of storage (12-month). The tablets formed from E. parviflorum Schreb. extract with chitosan can be included into preparations of sustained release time of the biologically active substances.

The increasing interest of the technology of drug form in natural biopolymers has become the reason for undertaking investigations on the possibility of guar gum application in the prescription of oral solid form of a drug. Alternative compositions and technology of the production of tablets of regulated in time sodium ibuprofen release were worked out for children. Two series of tablets were prepared with guar gum (5 and 10% content) and a series without the biopolymer. The tablet mass in each case contained keryostatic sorbitol and bioadhesive polyvinylpyrrolidone. All tablets were tested as regards the quality of production, compliance with the requirements of Polish Pharmacopoeia VI and potential therapeutic usefulness, manifestation of which is pharmaceutical availability of the therapeutic agent (sodium ibuprofen). The tests demonstrated that the produced tablets with sodium ibuprofen have proper physicochemical properties, in compliance with Polish Pharmacopoeia VI requirements. Application of biopolymer of guar gum type as adjuvant substance contributes to the improvement of the tablet hardness parameters and prevents technological problems (lining mixture of powders to tableting machine punch). The designed tablets demonstrate proper pharmaceutical availability of over 80%. Introduction of guar gum into their prescription prolonged their disintegration time and the rate of sodium ibuprofen release, which predisposes the produced form of a drug to have the function of a tablet with slowed-down release.