Iranian Journal of Pharmaceutical Research
Year:2003 | Volume:2 | Issue:1|Papers Count:15

Peptide and protein drugs have found an important position in therapeutics. Recent advances in pharmaceutical biotechnology have led to an increase in the number of protein products in the market. As these therapeutic proteins and peptides are made available, it will be essential to formulate these drugs into safe and effective delivery systems.The twenty different naturally occurring amino acids join with each other by peptide bonds and build polymers referred to peptides and proteins. Although the distinction between peptides and proteins is arbitrary, a peptide contains less than 20 amino acids, having a molecular weight less than 5000, while a protein possesses 50 or more amino acids and its molecular weight lies above this value.

g -Aminobutiric acid (GABA), the major inhibitory neurotransmitter in the central nervous system has two major receptor subtypes (GABAA and GABAB). GABAB receptors are activated by the antispastic and muscle relaxant agent, Baclofen, which is a lipophilic derivative of GABA. Since 1962 several strategies have been reported for the synthesis of baclofen. In this study an approach has been made to synthesize baclofen in an alternative way. The key steps involved the condensation of p-chloro benzaldehyde with nitromethane and the reaction of b-nitro styrene thus prepared with malonate diethyl ester. Further reduction and decarboxylation of the product gave access to baclofen with a good yield.

In order to identify the risk factors (predictors) of re-hospitalisation for high-risk asthmatic patients, a retrospective logistic regression analysis describing the relationship between the probability of re-admission and possible predictors in hospitalised asthmatics, aged over 5 years, between 1994-1998, was designed. Study setting was a district general hospital in the West Yorkshire, UK. The results obtained showed that there was a 25.5% re-admission rate for 440 patients admitted to the hospital during the period of study. Multivariate logistic regression analysis using the forward stepwise method revealed that only sex (OR=2.65, 95% CI: 1.42, 4.92), Jarman score (OR=2.03, 95% CI: 1.13-3.65) and allergy (OR=1.88, 95% CI: 1.06-3.32) could remain in the model as significant risk factors.It could be concluded that female patients, patients registered within the practices with a higher workload (higher Jarman score) and those who has a history of allergy were at a higher risk of re-admission. More attention should be paid to these patients who are in a higher risk of hospitalization.

Platinum is a metallic element, which may react with our cellular component through its involvement in cancer chemotherapy medications. Cisplatin is one of the most useful antineoplastic drugs against human ovarian carcinoma, which has the central element of platinum in its structure. The nature of chemical interaction between platinum and cellular macromolecules is yet to be understood. We examined the interactions of platinum with human ovarian OV 2008 cancer cells by infrared spectroscopy, through the exposure of this cell line to cisplatin. These studies showed that there was an interaction between cisplatin and DNA and proteins. Nature of these interactions and their possible effects are discussed in this paper. In summary, it has caused denaturation of proteins and modification of the interchain packing of the DNA. Our results show that infrared spectroscopy is a potentially useful technique for monitoring the interaction of elements and drugs with cell components.

Effects of venom from black scorpion Androctonus crasicuda (AC) were determined on isolated chick biventer cervices nerve-muscle and mouse hemidiaphragm preparations using twitch tension method. The isolated nerves were stimulated by electrical stimulator and response to each stimulus was recorded. The venom mainly acted prejunctionally to facilitate neuromuscular activity due to an increase in acetylcholine release.

In this study, attempts were made to evaluate the effect of various acrylic acid based Carbopols on the release profile of a beta-adrenoreceptor blocking drug, propranolol HCl, from matrix-type tablets invitro. For this purpose, tablets containing 160 mg of propranolol HCl along with various amounts of Carbopols 934 (C934), 971 (C971), 974 (C974) and Pemulen (Pem) were prepared using the wet granulation technique. Tablets prepared were placed in a USP apparatus I dissolution tester containing a pH 1.5 HCl solutions for the first 2 h of this study and a pH 6.8 phosphate buffer for the next 10 h of the study. The amount of drug released was determined using the constructed calibration curves at 289 nm, using a uv-visible spectrophotometer. The results showed that tablets containing Pem are unsuitable for preparing tablets with desirable drug release profiles. In contrast, C971, C974 and C934 were all found to be suitable for this purpose at concentrations of 14, 16 and 12%, respectively. Tablets containing C971 were found to have the slowest profile of drug release, while C934 containing tablets had the greatest drug release profile among the Carbopols investigated. Hence, Carbopols 971, 974 and 934 are found to be suitable, when used alone, for the preparation of propranolol HCl hydrophilic matrix-type tablets.

Plant materials have been found useful in decontamination of water polluted with phenolic compounds. The detoxification effect is due to peroxidases contained in plant tissue. Enzyme mediated oxidative coupling of phenol is followed by precipitation of the formed polymer and its removal from the aqueous phase. A synthetic wastewater buffered at pH=7.4 containing 0.9 mM phenol was treated in this research with cut Raphanus sativus root and its juice. Cut Raphanus or Raphanus juice were added separately as enzyme source to phenol solution in buffer and in tap water in two series of experiments. The reaction was initiated by the addition of hydrogen peroxide. After three hours stirring the phenol content of the mixtures was determined. More than 90% of phenol was removed in both cases.

The influence of various polymers on the release rate of lithium carbonate from matrix-type tablets was investigated in an attempt to formulate a sustained release solid dosage form. For this purpose, tablets containing 450 mg of lithium carbonate along with various amounts of Carbopol 934P, 971P, 974P, Pemulen and Eudragit RLPO as retarding agents and inactive ingredients (e.g. PVP, Avicel or starch) were prepared using wet granulation technique. Tablets prepared were initially placed in a phosphate buffer solution for 7 h and those formulations from which a minimum of 80% lithium carbonate released, were selected for coating process. The amount of drug released was determined by using atomic absorption spectroscopy. The dissolution rate of enteric coated matrix-type tablets were then evaluated in both acidic and basic mediums (1 h and 11 h, respectively). The results showed that Pemulen and Carbopol 971P are not suitable polymers for preparing tablets with desirable release profile, at all concentrations examined. However, it was observed that Carbopol 934P, 974P and Eudragit RLPO are capable of producing tablets with desirable release pattern, at concentrations of 2, 1.5 and 3%, respectively. Tablets containing Eudragit RLPO were found to have the greatest drug release profile, while Carbopol 974P showed the slowest release rate.

The volatile constituents of the aerial parts of vervain (Verbena officinalis L.) cultivated locally were investigated. Analysis of the volatile fraction by GC and GC-MS is described. Compounds were identified by various methods, the major compounds being 3-hexen-1-ol (7.28%), 1-octen-3-ol (32.76%), linalool (4.66%), verbenone (20.49%) and geranial (7.22%).

New analogues of nifedipine, as a known calcium channel blocker, were synthesized by replacing the orthonitrophenyl group on position 4 with 1- (4-Nitrobenzyl) -5-imidazolyl or 2-methylthio-1- (4-Nitrobenzyl) -5-imidazolyl substituent. Effects of the new synthesized compounds on blood pressure were studied at 15, 30 and 60 min after administration by indirect tail-cuff method and compared with nifedipine in male rat.The results indicate that all compounds reduce mean systolic blood pressure but their effectiveness is less than nifedipine. The onset of action of compounds 6c, 6d ,6e and 6g is also slower than the parent drug.

A topical o/w cream containing tretinoin microspheres was prepared. Gelatin microspheres of tretinoin were prepared using coacervation method. These microspheres contained about 50% w/w tretinoin. The particle size range of microspheres was between 90-150mm. In vitro drug release from microspheres and a cream formulation was studied. It was shown that drug release from microspheres followed Higuchi kinetics of release. However, drug release from the cream formulation followed zero order release profile.

Based on experiments showing immunomodulatory effects of garlic (Allium sativum L.), we sought to see whether Allium hirtifolim Boiss., belonging to the same genus of garlic, has any effect on immune responses.Hydroalcoholic extract and polyphenolic fraction of A. hirtifolium bulbs were prepared. Allicin (diallyl thiosulfinate), a biologically active component, was identified in plant bulbs by thin layer chromatography and determined by a spectrophotometery method at 412 nm. To study the effects of A. hirtifolium on acquired immunity, groups of Balb/c mice (n=8-12) were used. Sheep red blood cell (SRBC) was injected (sc, 1x108 cells/ml, 0.02 ml) and 5 days later hydroalcoholic extract (10-2000 mg/kg) and polyphenolic fraction (100-1000 mg/kg), betamethasone (4 mg/kg) or normal saline were given ip. After 1 h SRBC was injected to footpad (sc, 1x108 cells/ml, 0.02 ml) and footpad swelling was measured up to 72 h. To see the effects of A. hirtifolium on intrinsic immunity the same procedure was used, but animals just received one injection of SRBC after ip injection of tested compounds. Our results showed that the amount of total thiosulfinates and allicin in A. hirtifolium bulbs were 0.53% and 0.37%, respectively. Betamethasone inhibited paw thickness in both models. Hydroalcoholic extract and polyphenolic fraction of A. hirtifolium significantly reduced footpad thickness in both models (p<0.05). These findings showed that both hydroalcoholic extract and polyphenolic fraction of A. hirtifolium decreased acquired immunity response in a dose-dependent manner. However, only polyphenolic fraction of A. hirtifolium showed a dose-dependent effect on intrinsic immunity.

The constituents of the essential oil of Stachys laxa Boiss. & Buhse growing wild in Iran were investigated by GC-MS for the first time. Thirty-three constituents were identified. Germacrene-D (40.1%), b-caryophylene (16.7%), b-phellandrene (5.5%), caryophyllene oxide (4.6%), linalool (3.2%) and a-cadinol (2.6%) were found to be the major constituents of the oil.

The partial phase behavior of systems composed of lecithin/isopropyl myristate (IPM) /water or ketorolac tromethamine (KT) solutions (2.5, 5, 10 and 50% w/w) at various lecithin/IPM weight ratios (km) have been investigated by the construction of phase diagrams. A commercially available soybean lecithin (namely, Epikuron 200, phosphatidylcholine purity greater than 95%) was used in this study. Phase diagrams showed a narrow area of existence of a non-birefringent, transparent isotropic region along the lecithin / IPM axis in all systems, regardless of the km. The isotropic regions were stable for a minimum of 3 months at room temperature. The surfactant/oil ratio required for maximum KT incorporation has its minimum value in systems prepared with 50% KT solution, whereas the maximum value is obtained when a 2.5% KT solution was incorporated into the gel matrix. The results have also showed that for a given system, as km increases, the incorporation capacity increases. No significant differences in phase behavior were noted when altering the concentration of KT solution from 2.5-10%. However, a small decrease in the extent of the gel region was observed when 50% drug solution was incorporated into the system.

The arithmetic mean roughness, Ra, values were determined by scanning electron microscopic technique of different core models (furazolidone, nitrofurantion and acetyl salicylic acid), coated by HPMC film forming solution containing 10 wt% of various molecular weight PEGs. The results showed that both plasticizer molecular weight and core surface free energy could have a significant influence on Ra.