Füsun Acartürk

Calcium alginate microparticles for oral administration : I : Effect of sodium alginate type on drug release and drug entrapment efficiency

The natural polymers alginate and chitosan were used for the preparation of controlled release nicardipine HCl gel microparticles. The effect of the mannuronic/guluronic acid content and the alginate viscosity on the prolonged action of the microparticles, which were prepared with different types of alginates, were investigated. The mean particle sizes and the swelling ratios of the microparticles were also determined. The in vitro release studies were carried out with a flow-through cell apparatus in different media (pH 1.2, 2.5, 4.5, 7 and 7.5 buffer solutions). The release of nicardipine was extended with the alginate gel microparticles prepared with guluronic acid rich alginate. After the determination of the most appropriate alginate type, the effect of alginate-chitosan complex formation was studied on the release pattern of drug incorporated. It was observed that the alginate-chitosan complex formation reduced the erosion of the alginate-chitosan matrix at pH 7-7.5. The release of drug from the chitosan-alginate gel microparticles took place by both diffusion through the swollen matrix and relaxation of the polymer at pH 1.2-4.5.

Calcium alginate microparticles for oral administration: II. Effect of formulation factors on drug release and drug entrapment efficiency.

The release rate of nicardipine HCl from various alginate microparticles was investigated. Manugel A7B618 which has a high guluronic acid content of 70% and a low polymerization degree of 60-400 was used as alginate. A 2(3) factorial design was utilized for the preparation of the alginate microparticles. The effect of drug:polymer weight ratio, CaCl2 concentration and curing time on parameters such as the time for 50% of the drug to be released (t50%) and the drug entrapment efficiency were evaluated with analysis of variance. The mean particle sizes and the swelling ratios of the microparticles were determined. The in vitro release studies were carried out with a flow-through cell apparatus at different media (pH 1.2, 2.5, 4.5, 7, 7.5 buffer solutions). Drug:polymer weight ratio and the concentration of the crosslinking agent were the influential factors on the release of NC from the alginate microparticles. The release of nicardipine was extended with alginate microparticles prepared in a ratio of 1:1 (drug:polymer weight ratio). The release of drug from alginate microparticles took place by both diffusion through the swollen matrix and relaxation of the polymer at pH: 1.2-4.5. However, the release was due to diffusion and erosion mechanisms at pH 7-7.5.

Formulation and investigation of nicardipine HCl-alginate gel beads with factorial design-based studies.

The release rate of nicardipine HCl from various alginate gel bead formulations was investigated. The formulations were prepared by utilizing 23 factorial design. The effect of drug:polymer weight ratio, CaCl2 and sodium-alginate concentration on the time for 50% of the drug to be released (t50%) and the drug entrapment efficiency were evaluated with analysis of variance. The mean particle size and the swelling ratio of the beads were determined. The in vitro release studies were carried out by flow-through cell apparatus in different media (pH 1.2, 2.5, 4.5, 7 and 7.5 buffer solutions). Drug:polymer weight ratio and the interaction of drug:polymer weight ratio and CaCl2 concentration had a significant effect on the drug entrapment efficiency. The release of nicardipine was extended with the alginate gel beads, which were prepared in a ratio of 1:1 (drug:polymer). The release of drug from alginate gel beads took place both by diffusion through the swollen matrix and relaxation of the polymer at pH 1.2-4.5. However, the release was due to the diffusion and erosion mechanism at pH 7-7.5.

In-vitro and In-vivo Evaluation of Mesalazine–Guar Gum Matrix Tablets for Colonic Drug Delivery

The aim of this study was to develop colon-specific delivery systems for mesalazine (5-ASA) using guar gum as a carrier. A colon specific matrix tablet of mesalazine with guar gum was evaluated by in vitro and in vivo X-ray studies in humans. Two different types of guar gum were used in the experiments. Tablets were prepared by the slugging method. The physical properties of tablets were tested and in vitro release studies were performed by a flow-through cell apparatus with and without galactomannanase enzyme. The type and the amount of guar gum affected the in vitro release of drug from the matrix tablets. High viscosity guar gum, in the form of a matrix tablet was capable of protecting the drug from being released in the upper region of gastrointestinal (GI) system, i.e. stomach and small intestine. X-ray imaging technique was used to monitor the tablets throughout the GI system on 8 healthy volunteers. Barium sulphate was used as a marker in the tablets for in vivo studies. These results showed that, the matrix tablets reached the colon; not being subjected to disintegration in the upper region of the GI system in all the subjects.

Development of long-acting bioadhesive vaginal gels of oxybutynin: formulation, in vitro and in vivo evaluations.

Overactive bladder (OAB) and vaginal dryness are common problems after menopause. Oxybutynin (OXY) is an antimuscarinic agent that has been available for more than 30 years in the treatment of OAB patients. The aim of the work reported in this paper was to develop long acting mucoadhesive gel formulations of OXY and to investigate their effects on blood levels compared to those of oral OXY immediate release tablets, in rabbits. Mucoadhesive gels were prepared with chitosan, hydroxypropyl methylcellulose (HPMC K100M) and Poloxamer 407 (Pluronic F 127). The physicopharmaceutical properties of gels were evaluated. The gel formulation which was prepared with HPMC K100M, exhibited the highest viscosity, the greatest adhesiveness, cohesiveness and mucoadhesion values. The formulation which was prepared from HPMC K100M showed suitable permeation characteristics across the vaginal mucosa. Comparative bioavailability studies were carried out on rabbits with vaginal HPMC gel, vaginal chitosan gel, vaginal OXY solution and commercially available oral Üropan tablets. It was concluded that the highest AUC and relative bioavailability values were obtained for the bioadhesive vaginal gel formulation prepared with HPMC K100M. Therefore, the mucoadhesive vaginal gels of OXY can be a promising and innovative alternative therapeutic system for the treatment of OAB. It can be safely used in cases of overactive bladder and as well as vaginal dryness after menopause.

The effect of some natural polymers on the solubility and dissolution characteristics of nifedipine

Abstract The effect of natural polymers, such as water-soluble gelatin and egg albumin, on the solubility and dissolution characteristics of nifedipine has been studied. Comparison of such polymers was carried out by complexation with β-cyclodextrin. The interaction of nifedipine with these polymers both in aqueous solution and in the solid state was examined by performing solubility analysis, powder X-ray diffractometry and differential scanning calorimetry measurements. In addition, the surface tension of the samples was evaluated. Solid mixtures of nifedipine and polymer in various ratios were prepared by the kneading technique and their dissolution was carried out according to the dispersed amount method. It was found that water-soluble gelatin and β-cyclodextrin resulted in a significant increase in the rate of dissolution of nifedipine as compared to drug alone. Further, water-soluble gelatin may be particularly useful for the enhancement of dissolution of nifedipine.

Vaginal permeability and enzymatic activity studies in normal and ovariectomized rabbits.

AbstractPurpose. This study was initiated to develop an animal model, using ovariectomized rabbits, for the post-menopausal human, based on in vitro vaginal tissue permeability and aminopeptidase activity. Methods. An enkephalin derivative [D-ala2,N-methyl-phe4-glycol5][tyrosyl-3,5-3H] enkephalin {[3H] RX 783006), which has relative enzymatic stability to aminopeptidases and dipeptidyl peptidase, was used as a model peptide drug for permeability experiments. Aminopeptidase activity in vaginal homogenates, as well as in tissue pieces, was determined using 4-methoxy-2-naphthylamides of leucine, alanine, arginine, and glutamic acid as specific substrates. In addition, histological examination of normal and ovariectomized vaginal tissues was performed. Results. Vaginal permeability of the drug was significantly increased in the ovariectomized compared to the intact animal. The full vaginal tissue became thinner and mucosal epithelial thickness was reduced about twofold after ovariectomization and vaginal cells from the castrated rabbit were typically immature. Aminopeptidase activity, leucine aminopeptidase, aminopeptidase B and A, was the same in vaginal tissue homogenates and whole-tissue specimens in both normal and ovariectomized rabbits whereas the activity of aminopeptidase N was significantly decreased in ovariectomized as compared to normal rabbits. Conclusions. Based on the present data, the ovariectomized rabbit may be useful as an animal model for postmenopausal vaginal studies.

Rectal and vaginal administration of insulin–chitosan formulations: An experimental study in rabbits

Insulin is a polypeptide drug and it is degraded by gastrointestinal enzymes, therefore, it cannot be used via oral route readily. There are only parenteral forms available in the market. The aim of this study was to investigate the effect of rectal and vaginal administration of various insulin gel formulations on the blood glucose level as alternative routes in rabbits. Chitosan gel (CH-gel) was used as a carrier; the penetration enhancing effect of sodium taurocholate and dimethyl-β-cyclodextrin (DM-βCD) was also investigated. CH-gel provided longer insulin release. The maximum decreasing effect on blood glucose level was observed with insulin–CH-gel containing 5% DM-βCD. In conclusion, our results indicate that insulin may penetrate well through the rectal and vaginal mucosae from the CH-gel. DM-βCD was also found to be a useful agent to enhance the penetration of insulin through rectal and vaginal membranes.

Comparison of vaginal aminopeptidase enzymatic activities in various animals and in humans.

The specific enzymatic activity of four different aminopeptidases (aminopeptidase N, leucine aminopeptidase, aminopeptidase A and aminopeptidase B) in vaginal homogenates from rabbit, rat, guinea‐pig, sheep and humans was compared. The purpose of the study was to find an appropriate animal model that can be used in degradation studies of protein and peptide drugs. Different substrates were used as the relative specific substrates for the determination of aminopeptidase enzymatic activity: 4‐methoxy‐2‐naphthylamide of l‐alanine for amino‐peptidase N, 4‐methoxy‐2‐naphthylamide of l‐leucine for leucine aminopeptidase, 4‐methoxy‐2‐naphthylamide of l‐glutamic acid for aminopeptidase A and 4‐methoxy‐2‐naphthylamide of l‐arginine for aminopeptidase B. The vaginal aminopeptidase enzymatic activity of different species was determined spectrofluorometrically. The inhibition of aminopeptidase activity in the presence of bestatin and puromycin inhibitors was also investigated. The results showed the presence of aminopeptidase enzymatic activity in all vaginal homogenates in the order: sheep > guinea‐pig > rabbit ≥ human ≥ rat. Based on the results of the hydrolysis and inhibition of the 4‐methoxy‐2‐naphthylamide substrates, it was difficult to have an exact decision on the aminopeptidase type in the vaginal homogenates from the species studied. It was found that the aminopeptidase activity in rat, rabbit and humans was not statistically different. Therefore, we suggest that rats and rabbits could be used as model animals for vaginal enzymatic activity studies and for determination of the degradation of protein and peptide drugs in the vagina.

Effects of Epidermal Growth Factor on Lipid Peroxidation and Nitric Oxide Levels in Oral Mucosal Ulcer Healing: A Time-Course Study

PurposeEpidermal growth factor (EGF) has been used as a vulnerary agent. Epidermal growth factor accelerates wound healing. Nitric oxide (NO) is considered to be an important factor which is involved in wound healing. The objective of this study was to examine the effects of interactions between exogenous EGF and NOx which may have either similar or quite opposed properties in the process of oral wound repair on different days. In addition, lipid peroxidation was found to be an indicator of free radical damage.MethodsFive-month-old New Zealand albino male rabbits were used for this study. A surgical incision was made in the right mandibula diestema region of the rabbits, which were then divided into controls and EGF implanted groups. All parameters were analyzed by spectrophotometry.ResultsIn the EGF-implanted groups, both the NOx and lipid peroxidation indicator levels significantly decreased in comparison to those of the control groups on the first day after wounding. However, on the 3rd and 5th days after wounding, the NOx levels of the tissue strips also decreased in both modalities, but there was no significant alteration between the 3rd and 5th day after wounding.ConclusionIt was concluded that EGF affects oral wound healing by downregulating both the lipid peroxidation and NOx levels, and it may thus be considered to be an oxygen radical scavenger.