Influence of hydrogel structure on the processes of water penetration and drug release from mixed hydroxypropylmethyl cellulose/thermally pregelatinized waxy maize starch hydrophilic matrices.

The kinetics of water penetration and molsidomine release from both hydroxypropylmethyl cellulose (HPMC) and mixed HPMC/thermally pregelatinized waxy maize starch (SDWMT) hydrophilic matrices has been examined in 0.1 mol x dm(-3) HCl (pH 1.0) and 0.06 mol x dm(-3) Na3PO4/HCl buffer (pH 6.8). The rheological oscillatory test parameters of their gel layers obtained by swelling of the matrices in the two aqueous media have been observed. The kinetic swelling properties of mixed HPMC/SDWMT hydrogels (i.e. degree and velocity of both water penetration and swelling, transport mechanism which controls solvent sorption) directly influence the drug release behaviour and the structural features of the formed gel layer. Both diffusion processes are diffusion-controlled ones, their mechanisms being influenced insignificantly by the relaxation properties of the hydrated macromolecules. It has been established by means of comparative viscoelastic analysis, that mixed HPMC/SDWMT hydrogels demonstrate the typical behaviour of 'filled' composite systems having poor adhesion between the surface of the elastic SDWMT 'filler' and the continuous HPMC phase. Due to the inter-phase relations between the swollen starch granules and the linear cellulose derivative as well as to the specific structure of amylopectin molecule, the pregelatinized waxy maize starch shows a stronger influence on the velocities of both water penetration and drug release from mixed HPMC/SDWMT matrices.

Water uptake and relaxation processes in mixed unlimited swelling hydrogels.

The rheological oscillatory test parameters have been observed for highly concentrated hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose-sodium (NaCMC) and mixed HPMC/NaCMC hydrogels obtained by swelling of matrix tablets in 0.1 mol cm(-3) HCl and pH 6.8 phosphate buffer. The mechanical spectra of the gels have been analysed using theoretical models, i.e. a generalised Maxwell model and an adapted Maxwell model, both based on Ferry and Williams approximations. The relaxation time spectra as well as the parameters characteristic of linear viscoelastic behaviour have been calculated: zero shear viscosity (eta(0)), plateau moduli (G(N)(0), G(0)' and G(0)"), zero-relaxation time (tau(0)) and mean relaxation time (θ). The mechanical spectra of mixed HPMC/NaCMC hydrogels differ considerably from those of the pure ones, the type of the spectrum depending on the two polymers' ratios. In both media, the rheological models applied define the HPMC gels as homogeneous entangled networks, and those of NaCMC and mixed HPMC/NaCMC as heterogeneous physical gels. The relationship between the kinetic constants of water penetration and the mean relaxation times suggests that the molecular relaxation controls the water uptake velocity. With all the systems tested irrespective of pH of the aqueous phase, an inversely proportional dependence between the viscosity and the water penetration velocity has been noted. Since the degree of hydration is one of the factors determining the degree and velocity of drug release from the hydrogel matrices, the relation between the kinetic parameters of water penetration and the viscosity is a characteristic indicator for the gel structure, the degree of swelling and the drug release rate.

Development of model aqueous ophthalmic solution of indomethacin.

A new model aqueous solution of indomethacin was developed on the basis of Pluronic F68 (15%) and F127 (10%). They showed some practical advantages over the models prepared with polyols and polysorbate 80, which were used for comparison. It was found that both Pluronics acted very similarly and were more effective as solubilizers, created an appropriate viscosity, and formed reversible gels at higher temperatures, ensured the indomethacin chemical stability and prolonged in vitro drug diffusion, and showed high physiological tolerance on rabbit eyes. Moreover, indomethacin stability and solution viscosity in the presence of Pluronics did not change after heat sterilization (i.e., the samples can bear heat sterilization).

Regulation of the tetracycline hydrochloride release from polyacrylate microspheres. Part 1.

Due to the precipitation of free bases sparingly soluble in water, it is not possible to achieve a uniform release in the gastrointestinal tract of delayed action drugs containing salts of weak bases, e.g. tetracycline hydrochloride, at pH-values surpassing their pKa values. The problem of drug release control can be solved by adding Eudragit L to the polymetacrylate (Eudragit RS) microspheres. It has been established that 30% Eudragit L ensures a gradual uniform release of tetracycline hydrochloride (KOr = 11%/h) irrespective of variations in the pH of the gastrointestinal tract.

Biopharmaceutical studies of oral formulations containing propyphenazone.

Studies were performed with oral dosage formulations of propyphenazon, i.e. aqueous suspension (1%), instant suspension (1%) and tablets (100 mg) for pediatric use. The influence of the pharmaceutical adjuvants of the release of the drug from the model preparations was established. The biological availability determined from rabbits showed that the formulated preparations are biologically equivalent.

Biopharmaceutical investigation of rectal suppositories. Part 2(1): Pharmaceutical and biological availability of phenobarbital and phenobarbital-sodium.

The influence of the suppository base and drug solubility on the release an absorption of phenobarbital and phenobarbital-sodium from model suppositories was investigated. It was established that the pharmaceutical and biological availability of phenobarbital is higher from a hydrophilic base because of its improved solubility. The rate and the degree of release of phenobarbital-sodium are more significant from lipophilic bases. The bioavailability of two drug forms-phenobarbital and phenobarbital-sodium--is almost equal after rectal and oral administration.

Biopharmaceutical investigations of rectal suppositories. Part 1: Pharmaceutical and biological availability of theophylline.

The influence of suppository base and some tensides on the release and resorption of theophylline from model rectal suppositories was investigated in a preliminary way. It was established that the original Bulgarian suppository base Novosup ensures higher pharmaceutical and biological availability of theophylline in comparison with other investigated lipophilic bases. The preliminary inclusion of Tween 80 in Witepsol H 15 increased the pharmaceutical and biological availability of the drug. A linear relationship between the pharmaceutical and biological availability was observed after administration of model suppositories in rabbits.

[Toxicity, tolerance and blood concentrations of iron and tylosin with the use of preparation FV-82]. / Toksichnost, ponosimost i kruvni kontsentratsii na zheliazoto i tilozina pri prilagane na preparata FV-82.

A pharmacologic evaluation was made of a technologic model of a liquid drug form (code name phi B-82), having the following composition: tylosine tartrate 3500000 UI, cyanocobalamine 0.008 g, pyridoxin hydrochloride 0.500 g, tartaric acid 0.100 g, and feridextran (dextrofer-100) up to 100 cm3; pH from 5.5 to 6.5, and Fe3+ 100 mg/cm3. It was found that phi B-82 at i/m application to rabbits, subcutaneous injection to albino mice, and intra-abdominal introduction to albino rats and mice at rates that were equal to ED100 and 3 to 5 times higher than those used with pigs did not lead to local and total lack of tolerance. The acute toxicity (LD50) of phi B-82 at intra-abdominal application to 18-20 g albino mice was 29.2 cm3/kg. The single muscular application to guinea pigs at 2 cm3 per kg of body mass showed good absorption of the preparation - it did not differ essentially from those of dextrofer-100 and aquaous solution of tylosine tartrate used in equivalent amounts. The bacteriostatic concentrations of tylosine were maintained for 24 hours. It was shown that the optimal effect would be produced by a combined preparation having the qualities of the feridextrane complexes with a rapid absorption and those of the erythropoietic vitamins of the B12 group and B6 along with the participation of tylosine as an antibiotic.

Compatibility of a new suppository base with certain pharmaceuticals.

The compatibility of the macromolecular product Novosup-78 (mixture of polyethylene glycol esters with the free acids of sunflower oil and lard) with certain drugs relatively widely used in the suppository formulations was studied. By means of the solubility procedure and the UV spectral technique, significant interactions only with definite amounts from both components can take place. A predominant micellar solubilization in Novosup-78 solutions up to 0.5% was assumed. Taking into consideration the dependences obtained, it was concluded that the minimum ratio of drug to Novosup-78 in the proposed suppository formulations is not favorable for complexation interactions.

[On a possible mechanism of the gastrointestinal absorption of ionic drugs (author's transl)]. / Uber einen möglichen Mechanismus der gastrointestinalen Resorption ionischer Arzneistoffe.

An attempt was made to explain the mechanism of penetration of ionic medicinal substances through the lipoid membranes of the gastrointestinal tract. The equations worked out helped in the determination of constants which support and clarify further the already known concepts about the mechanisms of penetration of ionic drugs through the gastrointestinal tract.