ISSN: 7027-2221

Issue 5,

Issue 5

A study on factors affecting the preparation and in-vitro evaluation of mucoadhesive propranolol HCl suppositories


karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 1-15

Propranolol HCl is a beta-adrenoreceptor blocking drug which is subjected to extensive first pass metabolism after oral administration. In this study, attempts were made to prepare mucoadhesivesuppositories composed of 80mg (4%) propranololHCl by fusion method using fatty base,witepsolW-35 or water soluble bases polyethylene glycol (PEG) 4000 and mucoadhesivepoloxamer 188.
Physical characteristics and dissolution profiles of the prepared formulas were studied. The results showed that all the prepared formulas have acceptablephysical characteristics regarding weight variation, hardness, and melting time.
The release of drug from the prepared suppositories was found to be affected by the type of suppository base and additives. Fastest release was obtained with witepsolW-35 followed by PEG 4000 then poloxamer 188. Addition of carbopol 934 as a mucoadhesive polymer in a concentration of 1% or 2% to witepsol W-35 or PEG 4000 bases , retard the release of drug to unacceptable limit due to formation of an insoluble complex with the drug. On the other hand, the release of drug was enhanced by addition of propylene glycol to poloxamer 188 based suppositories in a concentration of 25% or 30% to a required limit for sustained release preparations that follow zero order kinetics.Furthermore, these last formulas were found to have mucoadhesive property.
Therefore, the results suggest that propylene glycol-poloxamer 188 mixture is a promising base for preparation of sustained release solid mucoadhesive propranolol HCl suppositories.

Investigation of the Interaction of Warfarin with Arginine and Thyroxine with Tyrosine.

Abd AL. Kareem Khaleel; Huda N. AL- Ania; Elham M. A. AL- Rufaie

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 16-23

Moleculer complxes of drugs (Warfarin and Thyroxine) with amino acids (Arginine and Tyrosine) were studied theoretically using PM3 Semi-empirical calculations of molecular orbital model and IR- techniques. The studied systems was: Warfarin with Arginine and Thyroxine with Tyrosine , The optimized geometry of the complexes showed interaction between drugs and Amino Acid molecules, the bending energies for these interaction varies from (- 4.194 to – 0.529) Kcal.mol-1. Which attributed to the formation of hydrogen bonding, and confirm experimentally by the IR- technique.

Study of some biochemical and immunological parameters in Iraqi benign prostatic hyperplasia and lower urinary tract symptoms patients

eman saadi saleh; mohammed muthana yousif; amal hamada ali

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 24-33

Benign prostatic hyperplasia (BPH) alone or with lower urinary tract symptoms (LUTS) was of the major public health problem among men especially over 55. In this trial serum interleukins six& eight (6&8) were estimated, also determining renal function test (urea& creatinine) and uric acid. Highly sensitive C- reactive protein (hs- CRP) and total prostate specific antigen (t- PSA) were measured in BPH, BPH+ LUTS and control groups. The result of this trial illustrate the elevation of all biochemical & immunological parameters significantly in both A&B groups when compared with control (P value= 0.002, 0.001 &0.000) except uric acid in group A appear insignificantly increased with group C (P value=0.477).
In conclusion the study predict the increasing in selected parameters very well & clearly so this help in diagnosis and management of BPH alone or with LUTS accompanies with inflammation which play an important role to transfer the benign disease to malignant. The aim of this study is to evaluate some clinical parameters especially hs- CRP that not previous used as a marker in the blood of elderly individuals who suffered from BPH with or without LUTS be of assistance in diagnosing & managing once in order to decrease the complication and severity of patient status which may convert the benign to malignant cases.

Hypolipidemic effect of date palm pollen and isolated flavonoids in sera of adult male rabbits

Al-Salihi; F.G; Majeed; A. H; R.R; Hameed

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 34-45

This study presents the effects of date palm pollen grains-DPP (Phoenixdactylifera) and isolated flavonoids on the level of cholesterol, triglycerides-TG, high-density lipoprotein cholesterol HDL-C, low-density lipoprotein cholesterol LDL-C and very low-density lipoprotein VLDL in sera of 49 adult male rabbits divided randomly into seven groups (7 animals in each group), in which G1, G2 and G3 treated with (30,60 and 90) mg/kg/day of DPP respectively, while the G4, G5 and G6 were treated with(7.5,15 and 30) mg /kg/day of isolated flavonoids from DPP respectively compared with non-treated group C1 as control. The results indicate that the level of cholesterol significantly decreased in sera of G1, G2 and G3, and also in sera of rabbits in G4 and G5as compared with C1, while the level of TG show slightly reduced in sera of G1,G3 and significantly increased in G6as compared with C1. In the other hand our results indicate that the important effect to improve the level of HDL-C may be due to the action of flavonoids at dose 15mg/Kg of body weight with no important effect of DPP to the serum level of HDL-C, and also reduced the levels of LDL-C in all groups treated with DPP and flavonoids, with no important effect to the level of VLDL-Cin sera of all groups.Our results also indicate that DPP grains and flavonoids have anti atherosclerotic effects in high dose. From all the above results we can conclude that pollen grains of date palm and its isolated flavonoids have hypolipidemic and anti atherosclerotic effects.

Preparation and Evaluation of Sodium Fluoride Orodispersible Tablets

Shaimaa N. Abd Al Hammid

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 46-55

Fluoride is used to prevent dental caries. Administration of fluoride tablet is an acceptable way for compensating the need for fluoride. The purpose of this study was to prepare orodispersible tablets of sodium fluoride and evaluation its physical properties as weight variation, hardness, disintegration, friability and release study. Different formulas of fast dissolving sodium fluoride tablets were prepared using direct compression method to enhance patient compliance using three different types of super disintegrants (sodium starch glycolate (SSG), croscarmelose (CC), and crospovidone (CP). Directly compressible mannitol was used as a diluent to enhance the mouth feel and compressibility, in addition to that, the prepared formulas were evaluated for hardness, friability, disintegration, dissolution time and content uniformity. Crospovidone was the best superdisintegrant used among croscarramelose sodium and sodium starch glycolate since crospovidone showed the fastest disintegration time (16±0.5, 15±0.5), and wettability (7± 0.5, 9±1) in F3, and F4 respectively, between croscarramelose sodium and sodium starch glycolate in addition to the acceptable hardness (4± 0.3), friability (0.962%) and taste also with dissolution time within 20 minutes and 55% drug release within 10 minutes for the selected formula F6. It was concluded that sodium fluoride can be prepared as orodispersible tablet using crospovidone as a superdisintegrant, manitol as a diluents and 15% sodium saccharine as a sweetener.

Intercellular adhesion molecules -1 (ICAM-1) and Vascular cell adhesion molecules-1 (VCAM-1) in hypertensive patients suffering from bacterial UTIs .

Nidhal abdul Mohaimen; Arif Sami; Zainab Thamer Showait Al-assady

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 56-68

Leukocyte binding to cellular adhesion molecules (CAMs) on the surface of vascular endothelial cells appears to be one of the earliest events in the atherosclerotic process. In this study the concentration of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on lymphocytes were evaluated during vascular disease like hypertension . In addition level of CAMs in hypertensive patients in response to other factors like sex, aging , smoking , anti hypertension drugs treatment (mainly with some β-blockers(propranolol) or ACE inhibitors(captopril)) and UTIs were also measured . As compared to controls mean of ICAM-1 and VCAM-1 were significantly elevated in hypertensive subjects. VCAM-1 was significant in male compared to female . Significant positive correlation was observed of VCAM-1 level in relation to ageing , Smoking and in hypertensive patients suffering from UTIs. While the level of both ICAM-1 and VCAM-1 was found to be decreased upon anti hypertension treatment with either β-blocker or ACE inhibitor decreased.

Effect of gender , aging , smoking and urinary tract infections on level of CD4+ T lymphocytes in hypertensive patients treated with propranolol and captopril drugs

Nidhal abdul mohaimen; Arif sami; Zainab Thamer showait al-assady; Ali jalil ali

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 69-80

Forms of adaptive response may be useful markers of endothelial activation and local or systemic inflammation. In this study the CD4+ T lymphocytes were evaluated during vascular disease like hypertension and the effect of other factors like sex, aging , smoking , anti hypertension drugs treatment (mainly with some β-blockers or angiotensin converting enzyme inhibitors) and urinary tract infections on expression of the CD4+ T lymphocytes were also studied . The results showed that mean level of CD4+ T lymphocytes was increased in hypertensive patients (p≤ 0.01) and this increase is more in female compared to male . Level of CD4+ T lymphocytes was significantly elevated in hypertensive subjects with age group of 30-40 years and the level started to decreased with aging. However, upon treatment with antihypertensive drugs (mainly β-blocker or angiotensin enzyme inhibitors) the level of CD4+ T lymphocytes was reported to decreased . CD4+T lympho-cytes level was significantly increased in hypertensive smoking patients(P ≤ 0.01) and in patients suffering from urinary tract infections (UTIs) .

Synthesis, Characterization and study of antibacterial activity in vitro of some hydrazones and formazan dyes containing benzothiazole moiety

Gazwan H.A. Al-Somaidaie

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 81-90

2-mercaptobenzothiazole (I) on treatment with hydrazine hydrate and HCl by two methods, µW and direct heating with solvent, give 2- hydrazinobenzothiazole (II), which on condensation by µW and direct heating with substituted aromatic aldehydes affords aryl substituted (1,3-benzothiazole-2-yl)hydrazone (III). The latter on treatment with aryl diazonium chloride at low temperature degree furnishes respective 1-(benzothiazol-2-yl)-5-(4-sub.phenyl)-3-arylformazan(IVa-e,Va-e,VIa-e)(formazan dyes) which on have been used as pigments for cotton, wool and white wood, and showed a significant value and also showed a resistance for primary washing process.
The antibacterial activities of these compounds have been assayed against various Gram -ve and Gram +ve organisms. The structures were elucidated and spectral behaviors were investigated with the use of 1HNMR, 13CNMR, FTIR, UV–Vis spectra .

Spectrophotometric determination of clioquinol via complex formation with Fe( III )in pharmaceutical preparations (creams) and environmental wastewater samples

Nief Rahman Ahmad; Ayad Mohamad Ali

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 91-99

To develop spectrophotometric method for the determination of clioquinol in pharmaceutical preparations and industrial wastewater samples. The method is based on the chelating of the drug with Fe( III) to form blue- green colored metal - chelate at room temperature which absorbs maximally at 639 nm. Beer' s law is obeyed over the concentration range of 2.00-20.00 µg/ml (6.5x10-6 - 6.5x10-5 M) with molar absorptivity and Sandell'҆ s sensitivity of 0.611x104 l/ and 5x10-5 mg/cm respectively, relative standard deviation (RSD) is less than 2.00% (n=10.00). The method is applied successfully for determination of clioquinol in some pharmaceutical formulations (creams) and industrial wastewater samples.

Biochemical study on the association of Selenium with hormone of thyroid gland in patients with thyroid disorder

Sahib Ali; Alaa frak; Hassan haider

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 100-105

In this study measured serum triiodothyronine (T3), serum thyroxin], serum thyroid-stimulated hormone (TSH), Selenium (Se) levels in 31 patients with hyperthyroidism, 26 patients with hypothyroidism and 40 control subjects. The concentration of Se was significantly lower than normal in hyperthyroidism and lower than normal in hypothyroidism. There was a negative correlation with TSH, and negative correlation with T3 and negative correlation with T4. The result of this study suggests that the concentration of Se is abnormal in thyroid disease.
Key Words: Hyperthyroidism, Hypothyroidism, Selenium

The Effect of Zinc Sulfate on Oxidative Stress and Lipid Profile Parameters in Male Rabbits Fed High Cholesterol Diet

Abdu Al-Razzak Abdu Al-Latif; Ali Faisal Jaber

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 106-118

Atherosclerosis is a chronic oxidative inflammatory disease characterized by deposition of lipids in the artery wall and infiltration of inflammatory cells. It is initiated, in part, by the interaction of oxidized low-density lipoprotein (oxLDL) with cells of the vascular wall. Atherosclerosis is the leading cause of mortality in developed countries and it is overwhelmingly contributes to approximately half of all deaths in the Western world than any other disorder. Zinc is an essential trace element that is vital in maintaining normal physiology and cellular functions. It has a potent antioxidant and anti-inflammatory action and it is used in treatment of various diseases in different systems in the body. This study was undertaken to evaluate the effect of zinc sulfate on prevention and progression of atherosclerosis in male rabbits fed high fat diet. A 32 male rabbits were enrolled in this study, divided randomly into four groups with 8 rabbits in each one. The first group, normal control group was supplied with standard chow diet for two month. The second one, hyperlipidemia-induced group was fed additionally to the standard chow diet, with a 1% (w/w) cholesterol powder. The third and fourth group, 220 mg and 440 mg zinc sulfate-treated group, was fed as group two plus 220 mg and 440 mg zinc sulfate respectively. Blood samples were collected and used to determine the concentration serum of lipid profile parameters, serum malonodialdehyde (MDA), and serum reduced glutathione (GSH) at day 0, 30 and 60. In hyperlipidemia-induced group the serum concentration of lipid profile parameters and MDA highly significantly increased while the serum concentration of GSH was significantly decreased compared to normal control group (p<0.05). Zinc sulfate did not significantly affect lipid profile (p>0.05) but instead its dramatically improved oxidative stress parameters as it significantly lowered the MDA level and increased GSH level compared with hyperlipidemia-induced group (p<0.05). From these results, we can conclude that the dose of 220 and 440 mg day of oral zinc sulfate for 60 days has a significant antioxidant effect in male rabbits fed high cholesterol diet.

Study The Effect of Soluble Beta Glucan of Saccharomyces cerevisiae on Protein Concentration of Human Circulating Blood Lymphocytes

Ali J. Jabber

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 119-130

This study was designed to detection the effect of the soluble beta glucan (ß-glucan) local and commercial extracts (LE , CE) of the Saccharomyces cerevisiae on protein concentration of human circulating blood lymphocytes at the concentrations (5 , 50 , 500 , 1000 ) µg/ml .The results showed significant differences increase on protein content at the level (P<0.05) for both effect of beta glucan Local extract , Commercial extract , and the best effect on protein lymphocytes concentration demonstrated at the highest concentration of the LE and CE .The four concentrations of β-glucan (5 , 50 , 500 and 1000 µg/ml) caused significant differences (p < 0.05) in protein content of lymphocytes secretion that treated with Local and Commercial extracts which represented (45.90, 63.18, 83.2, and 184.1)µg/ml and (32.27 , 50.45 , 79.54, 164.1) µg/ml respectively , as a compared to their control negative and control positive (58.63 ; 110.45) respectively µg/ml . While the values of both treatment at concentration (5,50,500)µg/ml is lower than control group that treated with (PHA) was represented (110.45) µg/ml . The concentrations 1000 µg/ml of LE, CE have best effect on protein concentration of lymphocytes secretion when compared with the control groups .

Synthesis and Antimicrobial Activity Study of Several New Tetrachlorophthalimides Substituted With Different Heterocycles

Ahlam Marouf Al-Azzawi; Kafa Khalaf Hammud

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 131-148

A series of new tetrachlorophthalimides linked to different Heterocycles including (thiazole, benzothiazole, thiadiazole, pyridine, and quinoline) were synthesized and followed by their antibacterial and antifungal screening. The synthesis of the new imides was performed via two steps, the first one involved preparation of a series of N-substituted- tetrachlorophthalamic acids via reaction of tetrachlorophthalic anhydride with different heterocyclic primary amines. Dehydration of the prepared tetrachlorophthalamic acids by treatment with acetic anhydride and anhydrous sodium acetate in the second step afforded a series of the desired N-substituted- tetrachlorophalimides. Biological activities of the prepared imides were evaluated and the results showed that these compounds have good biological activity.

Synthesis and study the Biological Activity of some new bis Maleimide derivatives containing 1 ,3 ,4- Oxadiazole ring

Ahmad S.H. AL- Janaby; Khalid M.M. AL-Janaby; Fawzi H.J. AL-Obaidy

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 149-169

This paper contains the synthesis of some new bis heterocyclic compounds starting from the esters of bis carboxylic acid which then converted to its hydrazide [1-5] then to bis1,3,4-Oxadiazole derivatives [6-10] beside bis maleamic acid derivatives [11-15] and finally with bis maleimides [16-20] .
Preparing of bis ester by usual esterification of substituted bis aliphatic carboxylic acid with absolute ethanol in acidic medium , then has converted to its substituted bis aliphatic carboxylic acid hydrazide by reacting it with hydrazine hydrate . The derivatives bis-1,3,4-Oxadiazole have synthesized by cyclization of bis aliphatic carboxylic acid hydrazide with 4- amino benzoic acid in presence of phosphoric acid 85% .
So ,the bis- maleamic acids have been synthesized by the reaction of compounds [6-10] with maleic anhydride in diethyl ether. Also bis maleimides are synthesized by cyclization of bis maleamic acids derivatives by using acetic acid anhydride and anhydrous sodium acetate. The synthesized compounds were identified by spectral methods UV,FT-IR and H1- NMR beside melting point and the purity was determined by using ( TLC ) and some of its physical properties were measured . Some of these compounds are tested against four strains of bacteria ( Staph. aurease , E. coli ,Sal. thph and Ps. aeruginosa)

Spectrophotometric Determination of Salbutamol by Oxidative Coupling Reaction with N, N- Dimethyl para phenylene diamine dihydrochloride in the Presence of Potassium Ferricyanide in Basic Medium

Ali Ibraheem Khaleel; Mohsin Hamza Bakir; Aziz Salih Aziz

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 170-182

This research involves a simple, rapid and sensitive spectrophotometric method for the determination of Salbutamol . The method based on the oxidative coupling reaction of salbutamol with N, N- Dimethyl para phenylene diamine dihydrochloride( DMPPDAD) using Potassium Ferricyanide as oxidizing agent in alkaline medium to form a water soluble product , that is stable and has a maximum absorption at 643 nm. pH between 10.7 -11.7 . at temperature between 20-35 oC. Beer’s law is obeyed in a concentration range 5 to 25 µg / ml with a molar absorptivity of 5719.27 L.mol-1. cm-1, The product was stable for 40 minutes with relative error was 0 to - 0.36 % and a relative standard deviation of 0.78 to 1.96% ,DL= 0.29 µg / ml, RE=99.69% depending on the concentration of Salbutamol. The proposed method has been successfully applied to the determination of Salbutamol in inhaler solution

Partial Purification of phenylalanine hydroxylase from urine of patients with chronic renal failure

Al-Salihi; F. G; A. H; Shaker; AL-Taie; A. K

karbala journal of pharmaceutical sciences, Volume 4, Issue 5, Pages 183-194

This study include purification of Phenylalanni hydroxylase ( PAH) from patients urine with chronic renal failure. The purification steps include,protein precipitation with ammonium sulphate solution. And ion exchange chromatography by using (DEAE – Cellulose A – 50) as anionic exchanger . Then two isoenzymes (I,II) were seperated through gel filtration by using (sephadex G-200) with purification folds 20.5 & 23.7 respectivily .
the research also include the kinetics studies of the two partially purified isoezymes (I&II) . The Km values were 4 mM .The two isoenzymes shown an optimum pH at 7.2, and optimum temperature at 25 Cº.