Immobilization and release of etophylin from hydrogels, based on polyacrylic acid and macrodiisocyanates.

Hydrogels, based on polyacrylic acid and various macrodiisocyanates that contain polyethylene glycol, polypropylene glycol or polytetramethylene glycol in the main chain are synthesized. The obtained hydrogels are studied as possible polymer carriers of drug substances. Etophylin was applied as a model drug. It is exposed that the etophylin release rate from the hydrogel depends on the way of drug comprise in the polymer net, from its density from the chemical nature of the crosslinking agent and from the pH of the environment. The carried out studies let us to conclude that the obtained hydrogels are possible materials as drug carriers.

Development and characterization of cross-linked poly(malate) microspheres with dipyridamole.

Biodegradable cross-linked microspheres containing up to 63 wt.% of the active substance were obtained in a polycondensation process between D,L-malic acid and the tetrahydroxy compound dipyridamole. The in vitro release mechanism from biodegradable cross-linked microspheres has been studied. It was found that dipyridamole was released due to two-step hydrolysis of the ester bonds of the network. Initially, the only product of the hydrolytic degradation was found to be an oligomeric ester fraction with M(w)=1000 Da. The release of the free drug started after 8 days due to a further hydrolysis of the oligomers in solution. It was found that blood plasma enzymes in rats did not affect the hydrolytic processes. Biodegradable poly(malate) microspheres containing an anti-aggregating agent dipyridamole can be considered as a novel drug delivery system for a prolonged period of time implying a future parenteral application.

Study of Verapamil hydrochloride release from compressed hydrophilic Polyox-Wsr tablets.

This study deals with Verapamil hydrochloride release from tablets based on high molecular weight poly(ethylene oxide) (PEO). The drug release proceeds as a controlled diffusion (n=0.44-0.47), which rate is dependent on the molecular weight of PEO. Independent from it, under the conditions of the Half-change test, the drug release practically ceases after 4 h as a result of obtaining low soluble in the water base. The introduction of hydrophilic polymers with pH dependent solubility (Eudragit L, Eudispert hv and Carbopol 934) at concentrations of 10/50% with respect to PEO amount keeping constant the ratio drug: matrix insures relatively complete release both in alkali medium and under the conditions of the Half-change test. Meanwhile drug release kinetics also changes - the release of all models studied runs as a typical abnormal diffusion (a=0.66-0.87), i. e. like a diffusion-relaxation controlled process. The decrease in drug concentration leads not only to retarded release of the drug sample but also to changes in the kinetics of the process. At lower drug concentrations on the matrix from a typical abnormal diffusion it turns into a relaxation controlled diffusion (n(10%)=1).

Biodegradable cross-linked prodrug of the bronchial dilator Vephylline. 2. Kinetics and quantum chemical studies on the release mechanism.

Experimental thermodynamics studies and quantum chemical reaction path calculations on the hydrolytic degradation of Poly-vephyllinemalate microspheres in acidic and basic media were performed. It was possible to make a conclusion on the release mechanism of free Vephylline as follows: a hydrolytic cleavage of the ester bonds between molecular fragments of R,S-malic acid takes place and leads to a soluble oligoester fraction. Then, further hydrolysis of the ester bonds between the xanthine fragment and R, S-malic acid leads to the release of Vephylline as free base. The hydrolytic process takes place in acidic solution with rapid degradation of the ester bonds between the malic acid monomers and by far slower degradation of the ester bonds between the malic acid and Vephylline. In basic solution both steps of the hydrolysis are fast processes leading to a complete release of free Vephylline within 1 h. The process of Vephylline release is under entropic control. The experimental results are well correlated to the results obtained after kinetics investigation and after AM1 quantum chemically calculated energy barriers in the reaction path leading to the tetrahedral intermediates of the hydrolytic reactions. This conclusion is in good accordance with an indirect study on the release mechanism of Vephylline from its polymeric prodrug, paying attention to the biological response, reported previously.

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.

[Biopharmaceutic studies of a bioerodible nystatin unit]. / Biopharmazeutische Untersuchungen einer bioerodierbaren Nystatineinheit.

The release of nystatin from monolithic bioerodible system with pectin was studied. The process of both system degradation and drug release was expressed with an equation of Hixon and Crowell. It was established that an increasing thickness of the system as well as an increase of drug concentration decreased the rate of erosion and the release of the active principle. Both the concentration of the plastificator and the temperature of drying the system in the range of investigation did not change these processes.

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.