Iraqi Journal of Pharmaceutical Sciences ( P-ISSN: 1683 - 3597 , E-ISSN : 2521 - 3512)

Formulation and Evaluation of Silymarin Microcrystals by In- Situ Micronization Technique

2019-11-16T17:05:05+00:00

Silymarin (SM) is a plant extract obtained from Silybum marianum( milk thistle) . It is class II type drug according to Biopharmaceutics Classification System with low bioavailability due to its low solubility.

Micro/nanonization during crystallization, surface modification and crystal structure modification may improve the dissolution rate of poorly water-soluble drugs.

The aim of this study was to increase the water solubility and dissolution rate of SM by in-situ micronization using solvent change either by stirring or ultrasonic method. Stabilizers like Gelatin, PVP-K30, HPMC15, Pulullan were used to stabilize the prepared ultrafine crystals. Effect of type and concentration of hydrophilic polymer, solvent: antisolvent volume ratio and the effect of ultrasonic irradiation were studied. The prepared microcrystals were evaluated for their %yield, water solubility, crystals structure by XRD,DSC, and SEM. Particle size and dissolution rate were also tested . Silymarin microcrystals prepared by ultrasonic method and stabilized by 0.1%gelatin using 1:2 solvent: anti-solvent volume ratio showed the best results with particle size reduction from mean diameter of 1.5µm (untrated silymarin) to 0.43µm with uniform morphology and enhanced solubility and dissolution.

Possible Amelioration of the Severity of Nutritional Steatohepatitis by Guggulsterone in Mice

2019-11-16T17:05:05+00:00

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, which characterized by steatosis, inflammation, and fibrosis. The aim of this designed study is to evaluate the ability of guggulsterone to prevent high fat diet induced steatohepatitis in mice. Five groups of male mice were selected and treated as the following: group I, mice had free access to standard commercial diet and considered as control group, group II, mice were fed a specially formulated high-fat diet for 12 weeks to induce non-alcoholic liver disease, while groups III, IV and V the mice were administered high fat diet containing guggulsterone at 500, 1000 and 2000 ppm concentration respectively for 12 weeks. Maintaining mice on fat rich diet only resulted in inducing the metabolic and histological NAFLD associated. While the treatment with guggulsterone significantly improves the evaluated markers. These results demonstrate guggulsterone may be useful in preventing the development of steatohepatitis.

Preparation and Evaluation of Rebamipide Film using Casting Technique for Local Action

2019-11-16T17:05:04+00:00

Abstract

The aim of this study was to prepare rebamipide ocular inserts in order to extend its release on the ocular surface for dry eye treatment. Solubility study was applied to the drug with or without l-arginine using different solvents. Solvent casting technique was used to prepare the inserts; l-arginine was used to solubilize the drug, hydroxypropyl methylcellulose grades (E5 and K15M) and poly ethylene glycol 200 were used as excipients. The inserts were evaluated for their physical and mechanical properties, moisture loss% and absorption %, surface pH, and in-vitro drug release. The use l-arginine exhibited an enhancement of rebamipide solubility in both deionized water and phosphate buffer (pH 7.4) by approximately 250 times and 3 times, respectively. The formulations showed uniform weight and thickness except for F1, and all showed uniform drug content. The absence of plasticizer in F1 caused haziness in its appearance and brittleness of the inserts. F3 which contain hydroxypropyl methylcellulose K15M showed good physical and mechanical properties thus was selected for in vitro release and was compared to the marketed brand Mucosta^® suspension eye drop; F3 showed significant enhancement in extending the release of rebamipide compared to the reference marketed brand.

Keywords: Rebamipide, L-arginine, Ocular insert, Solvent casting technique

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The Protective Effect of Ethanolic Extract of Mentha spicata Against Irinotecan-Induced Mucositis in mice

2019-11-16T17:05:04+00:00

Irinotecan induced-mucositis is an inflammatory event of intestine caused by an increase in concentration of active metabolite 7ethyl10-hydroxycamptothecin (SN38) in the intestine. Irinotecan must first be converted by a carboxylesterase (CES) to the active metabolite (SN38), which is subsequently glucuronidated by the hepatic enzyme to SN38G. The SN-38G is deconjugated in the intestine to SN-38 via ?-glucuronidase produced by the intestinal bacterial flora, which accounts for SN-38 delayed intestinal mucositis of irinotecan. To study the protective effect of mentha in irinotecan-induced mucositis, intestinal mucositis induced by I.P injection of irinotecan (75mg/Kg/day) for 4 days. Mentha ethanolic extract orally administered to mice for 7 days starting one day before irinotecan dose. Results showed that mentha ethanolic extract significantly decreased both jejunal tissue IL-1? (3.47±1.23 vs 6.5±0.36 ng/ml) and fecal ?-glucuronidase activity (79.78± 10.7 vs 120.6± 8.3 U) compared to model control group. Histopathological sections showed improvements in mucositis features in the mentha extract treated animals compared to the model control mice. As a conclusion, Mentha ethanolic extract has a protective effect on irinotecan-induced mucositis.

Evaluating Health-Related Quality of Life (HRQoL) in Iraqi Adult and Pediatric Patients with Beta-Thalassemia Major Using Two Different Iron Chelation Therapies

2019-11-16T17:05:03+00:00

Serum Aldosterone Levels in Patients With Diabetic Nephropathy in Relation to Vascular Calcification

2019-11-16T17:05:03+00:00

Diabetic Nephropathy(DN) is a complex disease manifested by persistence microalbuminuria occurring due to the interaction between hemodynamic and metabolic pathway that activates the local renin-angiotensin-aldosterone system resulting in a decline in renal functions.

This study aimed to quantify the associations between serum aldosterone concentration and fetuin- A as a marker of calcification in type 2 diabetic patients with and without microalbuminuria from one side, and study the possible relationship between aldosterone and fetuin-A with glycemic indices, serum electrolyte, renal function and microalbuminuria and body mass index from the other side.

A case-control study involved eighty-six adult subjects classified into three groups after testing urine microalbumin including thirty-two diabetics type 2 patients with positive microalbuminuria and twenty-eight diabetics type 2 patients with negative microalbuminuria and 26 healthy subjects during their visit to AL kindy specialized Center for Endocrinology and Diabetes / Baghdad. Those patients were compared to control group of 26 apparently healthy subjects, fasting blood samples was obtained from each of them in one occasion only to measure: fasting serum glucose, electrolyte, aldosterone, fetuin-A, urea, and creatinine. In addition to glycoheamoglobin, glomerular filtration rate and body mass index.

Despite the presence of microalbuminuria in thirty-two of the studied diabetics, there was no positive correlation between aldosterone and fetuin- A, besides that no significant variations in serum aldosterone ,glomerular filtration rate(GFR) values, while both groups showed a significant increase in fasting serum glucose and glycaoheamoglobin ,significant decrease in serum sodium and chloride in comparison with the control group , significant increase was detected in serum fetuin-A mean values in microalbuminuric diabetics. Whereas, negative microalbuminuric diabetics measures expressed a positive correlation between both serum sodium and chloride levels and fetuin -A.

The conclusion of this study diabetic patient are prone to vascular calcification
(VC) might be due to increase in aldosterone level or due to diabetic itself from this study we can conclude microalbuminuria can occur without a decline in renal function or a change in estimated GFR ,no definite correlation occur between aldosterone and fetuin- A, fetuin- A mean values are higher in diabetic patient with microalbuminuria compared to diabetic patients without microalbuminuria and control group and this referred to uncontrolled diabetes ,aldosterone show a correlation with weight and body mass index while fetuin- A does not show such correlation.

In general, electrolyte disturbances (hypernatremia) is more obvious in this study , and its occurrence is due to diabetic (osmotic diuresis) or drugs, while sodium retention which is a sign of aldosterone increment does not occur. Hypochloremia that occur in this study is due to chloride and it is in parallel with sodium level.

Preparation and Characterization of Etodolac as a Topical Nanosponges Hydrogel

2019-11-16T17:05:03+00:00

Nanosponges (NS) of etodolac(ETO) was prepared using the emulsion solvent diffusion method ; the effects of drug: polymer ratio, the effect of level concentration of internal phase and stirring time and other variables that effect on the physical characteristics of NS were investigated and characterized, The selected formula was lyophilized then incorporated into hydrogel ; which also evaluated .The results show that the formulation that contain Drug: PVA:EC in ratio 1:3:2 is the best with smallest particle size 40.2±0.098 with polydispersibility0.005 and in vitro release 97.6±0.11%, , ETO NS Carbopol hydrogel produced a significant(p<0.05) improvement of the in vitro release than pure ETO hydrogel.

Preparation and In-Vitro Evaluation as an Oral Microsponge Tablet of Baclofen

2019-11-16T17:05:02+00:00

The aim of the present study is to formulate floating effervescent microsponge tablet of the narrow absorption window drug, Baclofen (BFN) for controlling drug release and thereby decrease the side effect of the drug. The microsponges of BFN were prepared by non-aqueous emulsion solvent diffusion method (oil in oil emulsion method). The effects of drug: polymer ratio, stirring time and type of Eudragit polymer on the physical characteristics of microsponges were investigated and characterized for production yield, loading efficiency, particle size, surface morphology, and in vitro drug release from microsponges. The selected microsponge formula was incorporated into the floating effervescent gastro-retentive tablet. The prepared floating microsponge tablet was evaluated for tablet hardness, friability, swelling in addition to in vitro drug release. The results showed that the microsponge formula with Eudragit RS100 had optimum physical properties and controlled drug release (75% of drug release in 8 hr.) when compared with other formulas and pure baclofen. The oil in oil emulsion method is a promising method to produce baclofen microsponge.

Investigation of cytotoxic activity and dissolution improvement of Teniposide by incorporation into acid treated carbon nanotube and dispersed by hydrophilic polymer

2019-11-16T17:05:02+00:00

Single Walled Carbon nanotubes (SWCNTs), as nano-needle structures, are good candidates as nanocarrier delivery systems that carry drug to the site of action. They are good due to their unique pharmaceutical properties. Teniposide is an anticancer drug, which is widely used, but it has a problem of low solubility. In this study, to improve the properties of carbon nanotubes, pre-functionalization of carbon nanotubes via carboxylation with strong acids has been performed and then functionalized through attaching them to the polymer and copolymer. Concurrently, a proper polymer-copolymer combination has been selected by the UV-Visible spectrometer at 880nm. It is selected based on the qualitative dispersibility analysis, the visual observation of homogeneity, and separation tendency after centrifugation while quantitative estimation. The best formula is further studied utilizing FTIR, SEM, TEM, the solubility of Teniposide, and cytotoxicity through cell lines analysis.

The results show that the best dispersibility obtained in the formula that used PVA as polymer and PEO as copolymer at a ratio of 1:1. The solubility of incorporated Teniposide in the selected formula is increased by 11.5 fold and the cell line study shows significant improvement in cytotoxic activity of Teniposide. Accordingly, it can be concluded that the acid treated carbon nanotube and linked by polymer improve the pharmaceutical properties of the carrier and actively increase the potency of drug.

Status of CHADS2 and CHA2DS2-VASc Scores in Predicting Risk of Stroke and its Prevention in Iraqi Patients with Atrial Fibrillation

2019-11-16T17:05:06+00:00

Atrial fibrillation is associates with elevated risk of stroke. The simplest stroke risk assessment schemes are CHADS₂ and CHA₂DS₂-VASc score. Aspirin and oral anticoagulants are recommended for stroke prevention in such patients.

The aim of this study was to assess status of CHADS₂ and CHA₂DS₂-VASc scores in Iraqi atrial fibrillation patients and to report current status of stroke prevention in these patients with either warfarin or aspirin in relation to these scores.

This prospective cross-sectional study was carried out at Tikrit, Samarra, Sharqat, Baquba, and AL-Numaan hospitals from July 2017 to October 2017. CHADS₂ and CHA₂DS₂-VASc scores were manually calculated.

One hundred patients were participated, 48 were men and 52 were women. Their mean age was 62.56 ± 14.36 years. Permanent type of atrial fibrillation, palpitation, and hypertension were the most diagnosed type, symptom and comorbidity recorded in this study respectively. Average scores of CHADS₂ and CHA₂DS₂-VASc were 2.34 ± 1.39 and 4.1 ± 2.05, respectively. These scores were not calculated for these patients in hospital setting. Aspirin and warfarin were prescribed regardless to these scores.

The result of this study indicated that CHADS₂ and CHA₂DS₂-VASc scores were often neglected in hospitals; and aspirin is still widely used as a strategy to minimize the risk of stroke.

Keywords: Atrial fibrillation, CHADS₂, CHA₂DS₂-VASc, aspirin, warfarin.

Synthesis, Characterization and Preliminary Anti-inflammatory Evaluation of New Etodolac Derivatives

2019-11-16T17:05:06+00:00

Three new hydrazone derivatives of Etodolac were synthesized and evaluated for their anti-inflammatory activity by using egg white induced paw edema method. All the synthesized target compounds were characterized by CHN- microanalysis, FT-IR spectroscopy, and ¹HNMR analysis. The synthesis of the target (P1-P3) compounds was accomplished following multistep reaction procedures. The synthesized target compounds were found to be active in reducing paw edema thickness and their anti-inflammatory effect was comparable to that of the standard (Etodolac).

Synthesis and Preliminary Anticancer Evaluation of 6-Mercaptopurine –Methotrexate Conjugate as Possible Mutual Prodrug

2019-11-16T17:05:05+00:00

Small molecules drug conjugate mutual prodrug design (SMDC) composed of folate and lethal agent conjugate, rigidly bonded via hydrophilic bridge and self immolative disulfide bond ; represent new interesting approaches for cancer treatment , the component of SMDC intended for targeting folate receptor , along with greater conservation of component until reaching the target tumor tissue . The designing and synthesis of compound VI and VIII derived from 6-Mercaptopurine (6-MP) and Methotrexate ( MTX) conjugate altogether as mutual prodrugs were processed forward successfully by multistep reaction procedures , and by Thin Layer Chromatography (TLC) for preliminary detection of products and their intermediates, along with their purity. The structures of two final compounds and their intermediates were proclaimed by melting point measurement, infrared spectrometry and ¹HNMR analysis given results greatly correspond with theoretical proposed chemical structure of synthesized compounds. Furthermore, cytotoxic activity evaluation on cell line level had been done for two final compounds against human breast tumor cell (MCF-7) and human ovarian tumor cell (SKO-3) types of cancer cell line and the results were confirmed which show greater cytotoxic tumor activity of two final compounds, while compound VI possess optimal activity proportional with increased number of 6-MP molecules.

Synthesis of Acetylenic Derivatives of a Substituted 1, 3, 4-Thiadiazole as Antibacterial Agents

2019-11-16T17:05:01+00:00

Synthesis, Characterization and Preliminary Study of the Anti-Inflammatory Activity of New Pyrazoline Containing Ibuprofen Derivatives

2019-11-16T17:05:01+00:00

Synthesis, Characterization and Acute Anti-inflammatory Evaluation of New Mefenamic Acid Derivatives Having 4-Thiazolidinone Nucleus

2019-11-16T17:05:01+00:00

Mefenamic acid (MA) is one of the non-steroidal anti-inflammatory drugs, it is widely used probably due to having both anti-inflammatory and analgesic activity, the main side effects of mefenamic acid include gastrointestinal tract (GIT) disturbance mainly diarrhea, peptic ulceration, and gastric bleeding. The analgesic effects of NSAIDs are probably linked to COX-2 inhibition, while COX-1 inhibition is the major cause of this classic adverse effects. Introduction of thiazolidinone may lead to the increase in the bulkiness leads to the preferential inhibition of COX-2 rather than COX-1 enzyme. The study aimed to synthesize derivatives of mefenamic acid with more potency and to decrease the drug's potential side effects, new series of 4-thiazolidinone derivatives of mefenamic acid were synthesized IVa-g. The synthetic procedures for target compounds and their intermediates are designed to be as follows: acylation of secondary amine of mefenamic acid by chloroacetylchloride to produce compound (I), then reaction between compound (I) and hydrazine hydrate to form hydrazine derivative of mefenamic acid (compound II). After that, Schiff base formation by addition of seven benzaldehyde derivatives and finally, cyclization in presence of thioglycolic acid to form 4-thiazolidinone heterocyclic ring. The characterization of the titled compounds has been established on the basis of their spectral FTIR, ¹HNMR data, and by measurements of their physical properties. In vivo acute anti-inflammatory effect of the synthesized compounds was evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug produced significant reduction of paw edema with respect to the effect of dimethyl sulfoxide 10%v/v (control group). Compound IVe showed more potent effect than mefenamic acid at 240-300 min, while at time 300 min, compounds IVa and IVd exhibit more potent anti-inflammatory effect than mefenamic acid (50mg/kg, i.p.) as they reduced paw edema significantly more than mefenamic acid at mentioned intervals (p<0.05) . On the other hand compound IVc exhibited lower anti-inflammatory effect.