Development and in vitro/in vivo evaluations of bioadhesive buccal tablets for nicotine replacement therapy.

Buccal bioadhesive tablet formulations of nicotine hydrogen tartrate (NHT) for nicotine replacement therapy (NRT) were developed using chitosan and carbomer at different ratios. Magnesium hydroxide was incorporated into the formulations as pH increasing agent. In vitro release and bioadhesion properties of the tablets were investigated. Release of NHT from the tablets was increased with the increasing amount of chitosan in formulations whilst the bioadhesion of the tablet was decreased. In vivo studies were carried out in healthy, non-smoker volunteers in comparison to a commercially available transdermal patch. Plasma nicotine and cotinine levels were determined using gas chromatography-mass spectrophotometry. No significant difference was found between the maximum plasma nicotine concentrations (Cmax) obtained with the buccal tablet and the transdermal patch (p > 0.05). Time to reach the Cmax was 2.9 +/- 0.2 h and 11.5 +/- 1.3 h, and AUC0-24 values were 59.3 +/- 5.1 ng x h x mL(-1) (0-12 h) and 204.1 +/- 31.2 ng x h x mL(-1) for buccal tablet and transdermal patch, respectively.

Development of a buccal bioadhesive nicotine tablet formulation for smoking cessation.

Bioadhesive buccal tablet formulations for delivery of nicotine into the oral cavity were developed. Carbomer (Carbopol)974P NF) (CP) and alginic acid sodium salt (NaAlg) were used as bioadhesive polymers in combination with hydroxypropyl methylcellulose (HPMC) at different ratios. Magnesium carbonate was incorporated into the formulations as a pH increasing agent. In vitro release and bioadhesion studies were performed on the developed tablets. In the formulations containing CP:HPMC, the NHT released increased with the increasing HPMC concentration whereas a decrease was observed with increasing HPMC concentration in formulations containing NaAlg:HPMC. The bioadhesive properties of the tablets containing NaAlg:HPMC was not affected by the concentration of the NaAlg (P>0.05) but increased significantly with the increasing CP concentration (P>0.05). A decrease in pH of the dissolution medium to acidic values was avoided by incorporation of magnesium hydroxide into the formulations. The developed formulations released NHT for 8h period, and remained intact except for the formulation containing CP:HPMC at 20:80 ratio.

Percutaneous absorption of ketoprofen. I. In vitro release and percutaneous absorption of ketoprofen from different ointment bases.

Ketoprofen (KP) is a potent non-steroidal anti-inflammatory drug which is used for the treatment of rheumatoid arthritis. The oral administration of KP can cause gastric irritation and renal adverse effects. Topical application of the drug can bypass gastrointestinal disturbances and provide relatively consistent drug levels at the site of action. Since the efficacy of an ointment depends on the type of ointment base and the concentration of the drug, four different bases (white petrolatum, cold cream, hydrophilic ointment and Carbopol 940 gel) were used at 1, 3, 5, 7 and 10% concentrations of KP to evaluate the effect of ointment base and concentration. The general rank order of the drug release was found to be: Carbopol gel > hydrophilic ointment > cold cream > white petrolatum. There was a positive correlation between the concentration of KP and release rate for all bases except Carbopol gel. The in vivo percutaneous absorption of KP from different ointment bases at 3% concentration was studied by carrageenan-induced paw edema in mice. The rank order of the percent edema inhibition was as follows: Carbopol gel > or = hydrophilic ointment > cold cream > white petrolatum. There was a good correlation between the in vitro and in vivo results.

Effect of suppository bases on the release properties of a potent antimicrobial agent (C31G).

C31G is a specific formulation which contains equal molar concentrations of alkyl N-betaine and alkyl N,N-dimethylamine oxide. Vaginal suppositories containing 500 mg of C31G, this potent antimicrobial substance, were prepared by the fusion method in a variety of Suppocire and Witepsol bases with different melting points and hydroxyl values. In vitro release and diffusion characteristics of C31G from different suppository bases were investigated using two different systems. The release from suppositories was determined by using a system without a membrane and the diffusion rate of the released agent was determined through a semipermeable dialyzing tubing. Diffusion kinetics from suppositories were evaluated in terms of the apparent dialytic rate constants using the equation developed by Davis et al. From the results of in vitro studies, Witepsol H15 and Suppocire CM bases were selected as the most suitable ones for the formulations of C31G vaginal suppositories, since it is imperative for topical formulations to release the active substance in high proportions which are not absorbable by the mucosal membranes.

Topical effect of bromocriptine on rat-transplanted human prolactinomas.

In prolactinoma surgery, especially in macro-adenomas, it is not always possible to remove the tumour totally. Cell remnants may cause a regrowth and continue hypersecretion. In order to find out whether tumour remnants could be destroyed by local application of bromocriptine, a research model has been designed. First, prolactin secreting pituitary tumours, removed during surgery, were implanted bilaterally into the brain tissue of rats. In eight rats, the viability of tumour transplants was proven histopathologically and their prolactin secretion was shown immunocytochemically. In a second step, on eight rats, sterile bromocriptine solution was applied topically to the tumour transplants on one side. The other side served as control. Histopathological examination of these treated tissues revealed fibrosis. Immunocytochemical analysis showed no secretory activity. Ultrastructural investigations also revealed evidence of degeneration of the treated cells. The natural course of the transplanted tumour tissues of the other side, as a control group, was also observed during the same 55-day period.

A non-antibiotic antimicrobial mixture (C31G): evaluation of the antimicrobial efficiency of C31G on vaginal cultures.

Minimum inhibitory concentrations and the effective period for cidal concentrations of an amphoteric surfactant mixture (C31G) were determined on 13 microorganisms (common bacteria, strains ATCC, and fungi) by microtiter dilution procedure. Also the antimicrobial efficiency of this composition (C31G) was evaluated on 105 culture samples which were obtained from (Turkish) patients having vaginal infections. E. coli was found to be the most frequently observed microorganism (45.45%) in these samples and C31G was determined to be active on microorganisms obtained from vagina at low concentrations in a short time.

Evaluation of the interfacial properties of a new potent antimicrobial surfactant C31G.

The surface activity of a new potent antimicrobial mixture (C31G) of alkyl betaines and alkyl amine oxides were evaluated in order to determine the relationship between its antimicrobial effectiveness and physical properties. Therefore the surface tension measurements were performed at different temperatures using an interfacial tensiometer. Critical micelle concentrations, interfacial and thermodynamic parameters of C31G were obtained from the surface tension data.

Comparative bioavailability of three batches of four commercial acetaminophen tablets.

The aim of this investigation is to evaluate four brands of acetaminophen tablets and three batches of each brand for their in vitro properties and in vivo bioavailabilities using urinary excretion data. All batches dissolved at least 80% of their acetaminophen content within 30 minutes. The differences between the dissolution rates of the batches were not found statistically significant except the batches of brand C. With respect to their dissolution rates, the brands have the following order: A less than B less than C less than D. Statistical analysis of the percent bioavailabilities and the elimination rate constants showed that there was no significant difference between brands and or between the batches. The percent excreted in the first three hours was found to be significantly different between the solution and tablet A, between tablet A and tablet C, and between Tablet A and Tablet D.

Streptomycin sulphate microspheres: dissolution rate studies and release kinetics. I.

Targeting of drugs by microspheres, nanoparticles and liposomes is intended to increase the selective targeting to specific organs and to reduce their side effects. Streptomycin sulphate, a tuberculostatic antibiotic, is used as the active principle in this study. The aim is to accumulate the loaded microspheres in the lungs. The release of drugs associated with microsphere carriers has been found to be dependent on a number of factors. The aim of the investigation was to study the influence of the extent and nature of cross-linking, the type and the amount of the matrix material on the release characteristics of streptomycin sulphate microspheres. Human serum albumin and gelatin (Type B) were used as two different matrix materials. The crosslinking agents used were 2,3-butanedione and formaldehyde at different concentrations, and variable duration times. The in vitro release of streptomycin sulphate from microspheres is characteristically biphasic, with an initial fast release (the 'burst effect'), followed by a much slower release. Alteration in the characteristics of drug-loaded microspheres result in significant changes in the second (slow) phase of release. The release profiles of the different formulations has been studied and evaluated kinetically.