DARU, Journal of Pharmaceutical Sciences
Volume:10 Issue: 3, Autumn 2002

Abstract: Electrophoretic mobilities of salmeterol and phenylpropanolamine in capillary zone electrophoresis were determined using acetate buffer in mixed solvents containing different concentrations of water, methanol and acetonitrile. Maximum electrophoretic mobilities for salmeterol and phenylpropanolamine were observed with water-methanol-acetonitrile ratios of 5:50:45 v/v and 3:60:37 v/v, respectively, and minimum mobilities of both compounds occurred in methanol-acetonitrile ratio of 30:70 v/v. The generated experimental data have been used to evaluate a mathematical model to compute the electrophoretic mobility of the analytes in a ternary solvent electrolyte system. The proposed model is: ln μm =ƒ1 ln μ1+ƒ2 ln μ2+k ƒ3+M1ƒ1 ƒ2+M2 ƒ1ƒ3+M3 ƒ2ƒ3+M4 ƒ1ƒ²1+M5 ƒ²2ƒ3+M6ƒ²2ƒ3+M7ƒ1ƒ2ƒ3. Where μ is the electrophoretic mobility, subscripts m,1, 2 and 3 refer to mixed solvent and solvents 1-3, respectively, f is the volume fraction of the solvent in the mixed solvent system and M1-M7 and K are the model constants calculated by a least squares analysis. The generated experimental data fitted to the model and the back-calculated mobilities were employed to compute the average percentage deviation (APD) as an accuracy criterion. The obtained APD for salmeterol and phenylpropanolamine are 3.10 and 2.21%, respectively and the low APD values indicate that the model is able to calculate the mobilities within an acceptable error range.

Abstract: The aim of this study was to evaluate the effect of some important parameters on duration of adhesion of discs containing mucoadhesive polymers. For this purpose discs containing carbopol 934P (C934), polycarbophil (PC), sodium carboxymethyl cellulose (CMC) and hydroxypropylmethyl cellulose (HPMC) were prepared and the duration of their in vitro mucoadhesion were evaluated. Also the effect of the addition of various amounts of HPMC to other polymers, the effect of the test medium and prehydration of the test discs for 2 and 5 min prior to their placement in contact with the mucosal surface, on the duration of mucoadhesion of test discs were investigated. Results show that the addition of 25% HPMC increases the duration of mucoadhesion of all the tested polymers. The greatest duration of mucoadhesion with the anionic polymers CMC, C934 and PC was found to be at pH values above 4.0. The duration of mucoadhesion of HPMC containing discs were not greatly affected by the pH values above 2.2. However, at a pH value of 2.2 all of the investigated polymers showed the lowest duration of mucoadhesion. Finally, prehydration of discs containing HPMC, CMC or their combination before their placement on the mucosal surface resulted in a significant reduction in their duration of mucoadhesion. Discs containing only C934 or PC were far less affected by prehydration, especially after 2 min. Addition of HPMC to these discs greatly reduced their duration of mucoadhesion.

Abstract: Stimuli-sensitive polymers are suitable candidates for novel drug delivery systems, since they release drugs in a controlled manner in response to a stimulus such as temperature. In the present study temperature-sensitive polymer of N-isopropylacryamide (NIPAAm) was evaluated to modulate release of drugs with different molecular weights. Membranes of poly NIPAAm and its copolymers with acryl amide (AAm) were prepared by casting monomers, cross linker, and initiator between two glass plates with a defined spacer thickness. These thermo sensitive hydrogels that cross linked with N,N-methylene-bis-acrylamide (MBAAm) showed a swelling transition temperatures (37°C) that was used in the permeation control of hydroxy urea (HU) and erythromycin (Er). Permeation rates of the drugs in various temperatures were investigated. It was shown that the diffusion rate of HU and Er through membranes is increased with a decrease in temperature. This phenomenon may be explained by the swelling (hydration) properties of the polymers and the thermodynamic influence of temperature and may be used as on-off switching key for controlled release of different molecules.

Abstract: The pharmacokinetic behavior of amikacin and predictive performance of Sawchuk-Zaske dosing method, have been prospectively evaluated in 31 (16 male, 15 female) critically ill septic patients of mean (±SD) age of 58±23 years, mean ideal body weight of 59.6±6.4 kg, mean creatinine clearance of 52±21.5 ml/min, mean serum albumin of 3.1±0.5 mg/dl and median APACHE (acute physiology and chronic health evaluation) II score of 26 (with a range of 18 to 33). In this cross-sectional study, critically ill patients who met the Bone criteria for spesis but had stable creatinine clearance (serum creatinine change <0.5 mg/dl of the baseline) received the ordered dose of amikacin in one hour infusions. Blood sample were collected 30 minute after the third dose, half an hour before the fourth dose which was 1.5 times of the predicted half life of amikacin after the third dose. Cirrhotic patients and patients with renal failure requiring any mode of dialysis were excluded. Vital signs were recorded at each time of blood sampling; serum Mg+, serum albumin and APACHE score were recorded at the time of the first blood sampling. Mean (±SD) of the pharmacokinetic key parameters of amikacin in this population was as follow: Vd=0.390.045 l/kg; Ke=0.141±0.057 /h; half-life=5.7±2.06 h; Clearance=54.2±25.2 ml/min. There was a good correlation between Vd and serum albumin and also APACHE score II (r²=0.83, P=0.033;r²=0.82, P<0.001 respectively). Mean measured peak and trough amikacin concentrations were 20.9 and 3.2 μg/ml respectively which were significanthy different (P<0.05 paired t test) from levels, predicted by Sawchuk-Zaske method (33.5 and 4.6 μg/ml respectively). Ke, t½ and cledrane did not show any statistically significant changes (P>0.05 repeated measure test) amongst three times of blood sampling, but Vd was significanly different (P<0.05). The overall predictive performance of Sawchuk-Zaske method was poor; in spite of good correlation between predicted and measured parameters when using pooled data.

Abstract: In the present study the effectiveness of sodium cromoglycate in treatment of alveolar damage induced by chlorine gas in rats was investigated. Chlorine was generated by chemical interaction between potassium permanganate and concentrated hydrochloric acid. The rats were exposed to sublethal dose of chlorine gas. Treatment with 2.5 mg of 1 ml nebulized sodium cromoglycate solution over 5 minutes was initiated 30 minutes after exposure followed by twice daily treatment for 21 days. Results of this study show that cromoglycate reduced alveolar thickness, septal rupture, hemorrhage and detachment of the epithelial lining of the bronchioles induced by chlorine gas.

Abstract: In order to improve patient''s compliance in taking glycerine trinitrate (GTN) nylon hollow fiber which has been successfully used for release of chlorhexidine diacetate and levonorgestrel was employed to make nylon hollow fiber releasing GTN. Hollow nylon fibres of external diameter 0.63 mm, 75 mm long with an internal capacity of 16 μl, were filled with GTN (190 mg/ml) in 70% ethanol (v/v) or vehicle alone and the ends were heat-sealed. The fibers were then immersed in 10 ml of 0.9% (w/v) saline in a separating funnel. The GTN release pattern from fiber, the effect of the product on blood pressure and its potential dermal toxicity were assessed. The release of GTN from the fibres was approximately 2.7 μg/min when the fibres contained 16 mg of drug. The results showed that the amount of GTN within the single fibre was enough to reduce blood pressure significantly, while it did not show significant dermal toxicity. It is concluded that GTN fiber, if used as monofilament, is not an alternative method for GTN delivery.

Abstract: A group of racemic 3-[(2-hydroxyethyl), (2-Methoxyethyl), (2-acetylethyl) or (2-cyanoethyl)], 5- methyl, ethyl or isopropyl-1, 4-dihydro-2, 6-dimethyl-4-(1-methyl-5-nitro-2-imidazolyl)-3, 5-pyridinedicarboxylates [XIV-XXV] were prepared by the reaction of 1-methyl-5-nitroimidazol-2-carboxaldehyde [X] with acetoacetic esters [VI-IX] and alkys 3-aminocrotonate [XI-XIII]. In vitro calcium channel antagonist activities of the tested compounds were determined by their effects on contraction of Guinea Pig Ileal Longitudinal Smooth Muscle (GPILSM) which was induced by carbacol (1.67 χ 10^-7 M). All compounds exhibited calcium channel antagonist activity (IC50=10^-12 to 10^-13 M range) comparable to nifedipine as reference drug (IC50=1.07±0.12x 10^-11 M).

Abstract: Production of volatile sulphides in cell cultures of Allium porrum is described. Allium porrum calluses were initiated from whole seedlings. The high growth rate of Allium porrum callus was achived in Murashige and Skoog media containing only 1 ppm 2, 4-Dichlorophenoxy acetic acid. The routine method of solvent extraction of volatile sulphides was used for Allium porrum and the concentrated extract was subjected to capillary GC and GC-MS. Dipropyl disulphide and 4-methyl thiazolethanol were identified in A. porrum aggregated suspension cells.