فهرست مطالب

Iranian Journal of Pharmaceutical Research
Volume:4 Issue: 1, Winter 2005

  • تاریخ انتشار: 1383/12/25
  • تعداد عناوین: 9
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  • Fh Shirazi Pages 1-2
  • Mr Jaafari, M. Tafaghodi, Sa Sajadi Tabassi Pages 3-11
    The nasal cavity possesses many advantages as a site for drug delivery, such as, ease of administration, applicability for long term treatments and a large surface area for absorption. One important limiting factor for nasal drug delivery is the limited time available for absorption within the nasal cavity due to mucociliary clearance. Several drug delivery systems including different kinds of microspheres and liposomes have been tried for encapsulation of drugs and increasing the residence time in nasal cavity. In this study the clearance rate of three kinds of liposomes: neutral [phosphatidylcholin (PC) and cholesterol (Chol)], cationic (PC, Chol and stearylamine) and fusogenic (PC, Chol, dioleoylphosphatidylethanolamine) was determined by gamma scintigraphy with lactose powder being used as negative control.Liposomes were prepared by dehydration-rehydration method. 99mTc labeled liposomes were prepared using technetium pertechnetate in the presence of a potent reducing agent, stannus chloride. The labeling procedure was set in a manner that each 150 µl of liposome suspensions contained 2 MBq of radioactivity. Labeling efficiency was calculated by paper chromatography using acetone as mobile phase. Each delivery system containing 2 MBq of activity was sprayed into right nostril of four healthy volunteers and one-minute static views were repeated each half hour until 4 hours. Clearance rates were compared using two Regions of Interest (ROIs); the initial site of deposition of particles, and all of nasopharynx region. The clearance rate of each one of liposomes was calculated after applying the physical decay corrections.The mean labeling efficiencies for neutral, cationic and fusogenic liposomes were calculated as 91%, 20% and 69%, respectively. The cleared percent of preparations from nasopharynx region after 4 hours was determined as follows: neutral liposomes 18±2.9%; fusogenic liposomes 53.5±1.2%; cationic liposomes 69.7±4.2%; lactose powder 74.5±4.9%. Neutral liposomes showed the lowest clearance rate compared to lactose powder (P<0.0001), followed by fusogenic liposomes (P<0.01) and cationic liposomes (P<0.05). The clearance profiles of formulations from deposition ROI and nasopharynx ROI were identical.This study shows the neutral liposomes have the highest mucoadhesion properties and are suitable nasal delivery systems. Furthermore, this study proves that limiting step for the nasal clearance of nasally administered particulate systems is their dislocation from the initial site of deposition, and their following interactions with mucus layer in the rest of nasal passage does not significantly affect the clearance time.
  • N. Bolourtchian, F. Sattari Javid, S. Dadashzadeh Pages 13-19
    The effect of different kinds of surfactants in various concentrations incorporated in an inert matrix, on the release of procainamide hydrochloride, as a cationic model compound, was investigated in this study. Sodium lauryl sulfate and sodium stearate as anionic surfactants, cetyl pyridinium chloride and cetyltrimethyl ammonium bromide as cationic and span 60 and tween 80 as non-ionic surfactants were selected. Hydrophobic matrices were prepared using procainamide HCl, ethyl cellulose, dicalcium phosphate and different percentages of each surfactant and the dissolution rate of drug from various matrices was determined in pH values1.2 (for 2 h) and 7.2 (up to 10 h). The results showed that incorporation of anionic surfactants in matrix preparations resulted in a remarkable decrease in the release rate of procainamide HCl (P < 0.05), which was attributed to the formation of a poorly soluble complex between the cationic drug and the anionic surfactant. The formation of complex was confirmed by the precipitation titration test. On the other hand, presence of cationic surfactants considerably increased the drug release rate and it was noted that by raising the percentage of surfactant, a faster drug release rate release was achieved. With span 60 there was no change in drug release rate, probably due to its lower wetting capability. While in the case of tween 80, as a hydrophilic non-ionic surfactant, the drug release rate was increased, although statistically not significant. In general, it seems that the influence of cationic and non-ionic surfactants on drug release rate was in accordance with the ability of each surfactant in wetting the matrices and producing a greater number of channels for the dissolution fluid to leach out the drug. Kinetics evaluation of the release profiles showed that the Higuchi equation is the main model, fitting the data.
  • H. Montaseri Sayyafan, H. Tajerzadeh Pages 21-27
    Poly-(alkylcyanoacrylate) ester particles have been used for the preparation of different formulations ranging from ophthalmic delivery systems to cancer chemotherapy carriers in clinic. The aim of this study was to prepare and characterize poly-(methyl ethyl cyanoacrylate) (PMECA) particles containing 5-aminosalicylic acid (5-ASA). PMECA particles were prepared using the inverse emulsification polymerization technique. The effects of various formulation parameters such as dispersed phase volume, polymer to drug weight ratio, and surfactant concentration on loading efficiency and size of the prepared particles were investigated. The amount of drug was determined by UV spectrophotometery at 331 nm. Morphological characteristics of particles and particle size analysis were studied by Scanning Electron Microscopy (SEM) and Laser Light Scattering techniques, respectively. The results showed that there was no linear relationship between the dispersed phase volume (DPV) and loading efficiency of 5-ASA in the range of 20-50%. Increasing polymer/drug weight ratio in the range of 1-15, enhanced the loading efficiency from 11.4 to 78.2% in a linear mode (r=0.987). Increasing the surfactant concentration in the range of 1-3% did not increase the loading efficiency of the prepared particles, and increasing the concentration to 5% even decreased the loading efficiency of particles. Laser light scattering and SEM evaluations showed that in all prepared formulations, particles were in a mixture of micro and nanospheres and micro and nanocapsules and 50 percent of particles had mean sizes in the range of 6.4-10.1 micrometer. Although our results showed significant differences in the mean particle size between some of the prepared formulations, this variation was not practically important. It was concluded that by using proper conditions, it is possible to use PMECA as a polymeric matrix for loading of 5-ASA and the other hydrophilic drugs.
  • N. Naghdi, G. Mohaddess, S. Khamnei, M. Arjomand Pages 29-32
    Androgens have been shown to affect cognitive aspects of spatial memory. Testosterone which is the most important androgen, plays a role in the organization of behavior during development. Also, it has been shown that androgens cause sex related differences in learning and memory especially during neonatal period. In the current study, we assessed the effects of castration and testosterone enanthate (TE) administration on spatial cognition. Multiple doses of testosterone enanthate (20, 40, 80 and 120 mg/Kg) were examined on different groups using Morris water maze. Spatial memory was preserved in castrated rats. There was also no difference among multiple doses and control groups. For control of the level of testosterone in the blood of casterated rats and intact rats, blood samples were collected from intact group and 7, 10, 12, 14, 21 days after casteration. Testosterone levels were measured by Radio-immuno assay (RIA) technique and compared among all groups. The level of testosterone after 7 days in casterated rats were 0 nmol/L and after 21 days were 0.02±0.02 nmol/L while in intact rats were 2.69±0.88 nmol/L. These data suggests that changes in the level of androgen in circulation have no effect on spatial localization, at least after puberty in male rats.
  • M. Shekarchi, M. Binesh Marvasti, M. Sharifzadeh, A. Shafiee Pages 33-36
    Anticonvulsant activity of 7-phenyl-5H-thiazolo[5,4-e][1,2,3,4]tetrazolo[5,1-c]pyrrolo[1,2-a][1,4]diazepine (5) and 7-phenyl-5H-thiazolo[5,4-e][1,3,4]triazolo[5,1-c]pyrrolo[1,2-a][1,4]diazepines (6a-d) was measured against pentylenetetrazole (PTZ)-induced seizures in mice. Intraperitoneal injections of different doses (12.5, 25 and 50 mg/kg, i.p.) of test compounds decreased PTZ-induced seizure significantly in a dose-dependent manner.The test compounds were administered 30 min befor PTZ (80 mg/kg, i.p.) injection. The maximum response was obtained with 50 mg/kg of compound 6d that showed more anticonvulsant activity compared to diazepam (0.5 mg/kg). The frequency of mortality was also decreased by all listed compounds. Pretreatment of animals with flumazenile (as a benzodiazepine, BDZ receptor antagonist) decreased, but not completely inhibited the anticonvulsant activity of compound 6d (50 mg/kg). These results indicate that besides BZD receptors, other neurotransmitter systems may be involved in anticonvulsant activity of the tested compounds.
  • Mh Houshdar Tehrani, A. Zarghi, L. Erfani Jabarian Pages 37-41
    A new series of alkylthio imidazole analogues of captopril, an ACE inhibitor used in the treatment of hypertension, was designed and synthesized in order to obtain agents more active than captopril with less side effects. All the compounds thus prepared were purified and characterized by IR, NMR and Mass analytical instruments
  • Ga Khodarahmi, Py Chen, Gh Hakimelahi, Jw Chern Pages 43-56
    Several cycline dependent kinase 2 (CDK2) inhibitors with different chemical structures have been introduced. The hinge region of CDK2 (residues 81–84) contains a set of hydrogen bond donor and acceptor sites some of which must be satisfied for potent inhibitor binding. The benzimidazolone skeleton may provide such interactions. Accordingly, 3-sulfonamide substituted benzamido-benzimidazolones 24-31 were prepared starting from benzoic acid to give the acyl chloride 1 which was reacted with different amines to afford the acids 2-9. The acids were changed to their corresponding acyl chlorides 10-17. Reaction of 10-17 with o-nitropheyl hydrazine gave the nitro derivatives 18-25 followed by reduction of the nitro groups to give 26-33 which were then reacted with ethyl chloroformate to give the target compounds 34-41. The 3-pyridyl derivative 47 was prepared starting with chlorosulfonyl benzoyl chloride to give the acid 43 which was changed to the corresponding acyl, nitro and amino derivatives 44, 45 and 46, respectively, followed by the final ring closure reaction to give 47. The dibenzimidazolinoe derivative 49 was also obtained from the reaction of isopropenyl-benzimidazolone 48 and 3-chloro sulfonyl benzoyl chloride. The target compounds were then tested against the cancer cell lines, Hepa G2, HT-29, CL1-5 and AGS. Results indicated that the target compounds did not show reasonable cell growth inhibition comparing to the positive and negative controls.
  • A. Shafaati, M. Zand Karimi, Sm Foroutan, N. Hassani Oliaee Pages 57-60
    Capillary electrophoresis (CE) with indirect UV detection is an interesting analytical method for the analysis of drugs and pharmaceuticals. Good and reproducible capillary quality is needed to develop robust methods and to facilitate method transfer in CE. It is widely accepted that preconditioning procedures are indispensable in capillary electrophoresis in order to achieve reproducibility of migration times and peak areas.In order to explore different aspects of this technique, a set of experiments were performed using vigabatrin as a model drug. The effects of capillary rinsing between each run was investigated using basic (NaOH 0.1 M) and acidic (phosphoric acid 0.1 M)-wash cycles. The results of 10 consecutive injection of the model drug after each of the two wash cycles, reveal that more reproducible results obtained when acid-wash cycle was performed as a capillary conditioning protocol. The higher pH changes during basic-wash cycle and its effects on the characteristics of the capillary inner surface were suggested as a source of greater variation between consecutive runs.