Development of novel budesonide pellets based on CODES[TM] technology: In vitro/in vivo evaluation in induced colitis in rats

Budesonide is the drug of choice for treatment of active inflammatory bowel disease [IBD]. The aim of this study was to develop budesonide pellets based on a novel colon drug delivery system [CODES]. Pellet cores containing lactulose or mannitol were prepared by extrusion/spheronization and coated with an acid soluble polymer [Eudragit E100], hydroxypropylmethyl cellulose [HPMC] and an enteric coat [Eudragit FS 30D] sequentially. In vitro drug release of coated pellets was studied using USP dissolution apparatus type II in buffers of pH 1.2 [2 hrs], pH of 7.4 [4 hrs] and pH of 6.8 containing 8% rat cecal contents [RCC] [18 hrs]. The efficacy of the optimized formulation [containing 50% lactulose coated with Eudragit E [30% w/w] and Eudragit FS 30D [12% w/w]] was evaluated against 2, 4, 6-trinitrobenzenesulfonic acid [TNBS]-induced colitis in rats. The results of the kind of bacteria in vitro dissolution tests indicated absence of drug release in pHs of 1.2 and 7.4 and controlled release in buffer of pH 6.8 containing RCC. It was found that release rate was controlled by the type and amount of polysaccharide and the thickness of the acid soluble layer. The prepared formulation showed promising results in alleviating the conditions of experimental model of colitis. The results of this study suggest that pellets based on CODES technology could be useful for colonic delivery of budesonide

[Management of blunt hepatic trauma in patients referred to Isfahan Alzahra hospital during 1998-2008]

Liver is the most commonly injured organ in blunt abdominal trauma. Early diagnosis and appropriate treatment of blunt hepatic trauma would decrease morbidity and mortality rates. To achieve this goal, physicians should be aware of the prevalence, etiologies, signs and symptoms, diagnostic procedures and up-to-date management of blunt hepatic trauma. A descriptive retrospective study was conducted on all 130 patients admitted to the emergency department of Isfahan Alzahra Hospital during 1998- 2008. Data were collected from patients' medical records and analyzed using descriptive statistical methods. Out of 130 patients, 103 cases [79.2%] were male. Mean age of cases was 29.7 +/- 13.46. The most common traumatic mechanism was vehicle accidents in 100 cases [76.9%]. Sonography in association with CT scan as the most commonly used diagnostic method was obtained in 68 cases [52.3%]. Eighty-eight cases [67.7%] underwent surgery while conservative treatment was selected for the other 42 cases [32.3%]. Admission to ICU was more frequently needed in conservative treatment group [P=0.001]. The mean length of hospitalization was shorter for patients underwent surgery. Better clinical results and fewer complications in the group managed conservatively presents it as a safer and more efficient treatment method

[Prevalence of pathogens and antimicrobial susceptibility patterns in urine cultures of patients referred to Avesina medical center in Qazvin]

Knowledge of antimicrobial susceptibility is a suitable method in empirical use of antimicrobial agents. This study was designed to detect the prevalence and antimicrobial susceptibility patterns of urinary tract infections. This prospective study investigated the positive urine cultures of out-patients and inpatient of Avesina Teaching hospital in Qazvin during 3 months from July to September 2007. The antimicrobial Susceptibility Testing was performed by disk diffusion method. Among 224 urine samples, E coli was the most common species [61.2%] followed by Pseudomonas [10.3%], Kelebsiella [8.9%], and coagulase negative staphylococci [6.3%]. Nitrofurantoin [72.4%] and Amikacin [77%] were shown to be the most effective drugs on E coli species with Amikacin showing the highest efficacy on Pseudomonas species [50%]. E coli was the most common pathogen with maximum susceptibility to Nitrofurantoin. Hence, the administration of this drug in treatment of indoor and uncomplicated forms of UTI is recommended. Intravenously, Amikacin was found to be the most effective agent for such clinical complications

[Preparation of diltiazem topical gel for the treatment of anal fissure and in-vitro, ex-vivo drug release evaluations]

Anal fissures are small tears in the lining skin of the anus presenting with typical symptoms of pain and bleeding during defecation. Several new forms of medicines such as glyceryle trinitrate [GTN] ointments and diltiazem, a calcium channel-blocking agent, have been recently used for the treatment of these fissures. Diltiazem relaxes the muscle of anal sphincter and consequently increases blood flow to promote healing. It does not have GTN side effects like headache, anal burning and hypotension. The objective of this study was to formulate a suitable topical gel from diltiazem and then to investigate its physicochemical stability and also the drug release profiles from the bases. Various formulations of gel base including Guar 1.25%, Tragacanth 1.5%, HPMC 1%, and HPMC 1.5% were prepared and in vitro release and penetration characteristics of diltiazem from each preparation were studied through a hydrophilic dora pore diffusion barrier and membrane excised rat skin using Franz cell over a period of 5 hours. The amount of drug released from topical preparations was determined spectrophotometrically a lambda[max]=236 nm. Stability studies and shelf life assessments were performed too. Gel formulations containing HPMC, Guar and Tragacanth presented both good chemical and physical stabilities. The rates of cumulative drug release from HPMC 1%, HPMC 1.5%, Guar 1.25% and Tragacanth 1.5% bases using synthetic membrane were 89.7%, 76.7%, 94.9% and 66.1% respectively. For excised rat skin test, the cumulative percent of penetrated drug at the end of each experiment were 52.7%, 50.9%, 64.6% and 42.6% for HPMC 1%, HPMC 1.5%, Guar 1.25% and Tragacanth 1.5% bases respectively. The comparative study showed that the percent of drug release from synthetic membrane was more than the percent of penetrated drug through excised rat skin for all bases [P<0.05]. It was concluded that the kinetics of diltiazem release in vitro was not affected by the kind of gel forming agent and for all of the formulations, Higuchi's kinetic model was suitable to explain their kinetics

[Clinical evaluation of a topical doxepin cream [5%] in treatment of eczema]

Eczema is one of the most common pruritic skin disorders for which various treatments are used to relieve the symptoms. There are several reports about the efficacy and in part safety of topical doxepin in the treatment of pruritic dermal diseases. However, lack of a suitable topical preparation from this drug in our country persuaded us to design the present trial. A randomized, double blind, placebo controlled and multi- central clinical trial was carried out in Isfahan during the years of 1383-84 by using 60 volunteers and both the drug and placebo were given QID for 8 days. The efficacy, side effects and their relevance to sex and age of subjects were assessed before, during and after the treatment. The data were analyzed using non-parametric tests including Mann-Whitney, Wilcoxon, and Kendall Tau where appropriate. Results indicated that doxepin cream effectively reduced disease symptoms including pruritus [75.5%], inflammation [43.8%] skin dryness [37.5%] exudates [59.5%], lichenification [41.5%], and eczema [41.5%] after the course of treatment [the day of 8]. Same results were obtained by using placebo. Stinging as an adverse effect was occurred in both the drug [30%] and placebo [27%] groups. Although there was no significant difference between the two groups, it can be concluded that doxepin cream [5%] is effective in depressing the signs and symptoms of pruritic skin disorders. A larger clinical trial is needed to evaluate the efficacy and safety of the product more precisely

[Preparation and physicochemical evaluation of progesterone suppository]

Progesterone, the most important progestin in humans, is indicated in several conditions. Progesterone suppresses menstruation and uterine contractility that is very important for the maintenance of pregnancy. After oral administration, it is almost completely metabolized in the first passage through the liver and its intramuscular injection causes local irritation and pain. Therefore rectal or vaginal suppositories of progesterone are used in the treatment of premenstrual syndrome, puerperal depression [Cyclogest [R], 200-800 mg/day] and luteal phase defects[25 mg/12h] in patients with infertility and sterility. The main objectives of this study were to prepare different formulations of progesterone suppository in hydrophilic and lipophilic bases and to select the suitable formulation based on drug release from the bases. Hydrophilic [PEGs], hydrophobic [Witepsol H[35]] bases and additive ingredients were used to manufacture the suppositories. The replacement factor was determined and suppositories were prepared by using the fusion method. In order to control the physicochemical characteristics, various parameters such as weight variation, liquefaction time [Krowczynski method] and content uniformity were determined. Dissolution testing was done by dialysis cell method in dissolution apparatus [Pharmatest, PTSW3-Germany]. The amount of drug released during dissolution test was determined by using UV spectrophotometer at 241 nm. Content uniformity, weight variation and liquefaction times of manufactured bases were acceptable according to official pharmacopoeia [BP and USP]. Releasing profiles in normal saline containing 0.1% Sodium Lauryl Sulfate showed that the rate of release from PEGs formulations is faster than Witepsol bases. PEGs and Witepsol bases could be successfully used to prepare progesterone suppositories. In vivo bioavailability of progesterone after rectal and vaginal administration and the clinical assessment of the selected formulations are future plans

[Preparation and physicochemical evaluation of diazepam suppository in infantile febrile seizures]

Introduction and Objective: febrile seizures are the most common form of convulsions in childhood. Rectal diazepam in solution is very suitable for acute treatment of febrile convulsions. Furthermore, diazepam suppositories are used prophylactically. The aims of this study were to prepare a suitable and efficient formulation of diazepam suppository and to elucidate the influence of suppository base on dissolution rate using various techniques

Materials and Methods: suppositories containing diazepam [5 mg] were manufactured with Witepsol H35, PEG300 plus PEG4000, PEG1000 plus PEG4000 and PEG1000 plus PEG6000, by the fusion method. Physical characteristics of suppositories such as weight variation, liquefaction time, mechanical strength, content uniformity and percent of drug released were studied and compared to a brand of diazepam suppository. Dissolution testing was done by three methods: the USP basket, paddle and dialysis cell

Results: the results showed that the release of drug from PEG1000+4000, PEG1000+6000 and Witepsol H35 is greater than PEG300+4000 and brand one. In dialysis cell method drug was released slower than the paddle and basket methods

Conclusions: it was recognized that a dissolution testing method would be useful in both formulation design and also in quality procedures relating to the products

[Topical formulation of doxepin and ex vivo evaluation of drug percutaneous absorption in atopic dermatitis]

Introduction and Objective: atopic dermatitis [AD] is a chronic and inflammatory skin disorder characterized by erythematous, eczematous, and highly pruritic lesions. Topical corticosteroids and oral antihistamines such as hydroxyzine, diphenhydramine, and promethazine are useful for the control of pruritus. Doxepin, a tricyclic antidepressant, with potent H1, H2 and muscarinic receptor blocking activity has recently been licensed as a topical treatment [Zonalon® 5% cream] by the Food and Drug Administration [FDA] for the short term [up to 8 days] management of moderate pruritus in adults with atopic dermatitis and lichen simplex chronicus. The objective of this investigation was to evaluate the physicochemical stability of various dermatological preparations of doxepin. Furthermore, the Ex-vivo percutaneous absorption of drug profiles obtained from different formulations was compared

Materials and Methods: various formulations including W/O and O/W emulsions, and jelly base were prepared and the in vitro release and penetration characteristics of doxepin from each preparation were studied through a hydrophilic Dora pore diffusion barrier and membrane excised rat skin using Franz cell over a period of 6h. The amount of drug released from topical preparations were determined spectrophotometrically at [lamda]max =292 nm

Results: the obtained results showed that the prepared formulations presented both good chemical and physical stabilities. The generated rank order for the drug release from different preparations using membrane was observed to be doxepin cream 5%> doxepin gel. The Ex vivo penetration of doxepin through excised rat skin showed that the cumulative percent of penetrated drug at the end of each experiment were 75.5 % and 44.2 % for doxepin cream and doxepin gel respectively

Conclusion: the in vitro release kinetic of doxepin is not affected by the kind of topical dosage form [gel or cream]. The release of drug from both cream and gel formulations obeyed Higuchis kinetic model

In vitro - in vivo evaluation of sustained - release lithium carbonate matrix tablets: influence of hydrophilic matrix materials

Background: conventional Lithium carbonate [LC] tablets produce rapid and relatively high peak blood levels resulting in adverse effects. These drawbacks can be overcome by designing a suitable sustained or controlled-release LC preparation

Methods: sustained-release matrix tablets were therefore developed using different types and ratios of polymers including carbomer [CP], Na carboxymethylcellulose [Na CMC] and hydroxypropylmethylcellulose [HPMC], to assess the release profiles and in vivo performance of the formulations. The tablets were prepared by either direct compression [DC] or wet granulation [WG]. In the DC method, 69% [450 mg] LC, 5, 10 or 15% CP or Na CMC [of total tablet weight], lactose and /or Avicel [to maintain constant tablet weight] were mixed and directly compressed. In the WG method, 450 mg LC and 10, 20, or 30% HPMC were granulated with Eudragit S100 solution, dried, and then compressed to formulate the tablets. In vitro and in vivo, newly formulated sustained-release LC tablets were compared with sustained-release commercial tablets [Eskalith® and Priadel®]. In vivo studies were conducted in nine healthy subjects in a cross-over design, with a 3x3 Latin square sequence, and pharmacokinetic parameters were estimated using classical methods

Results: the matrix tablets containing 15% CP exhibited suitable release kinetics and uniform absorption characteristics comparable to that of Eskalith®. In vivo, this formulation produced a smooth and extended absorption phase very much similar to that of Eskalith® with the identical elimination half-life and extent of absorption

Conclusion: the matrix tablets containing 15% CP reduces the incidence of side effects often associated with high serum concentration of Lithium and blood level variations. Direct correlation between the dissolution profiles and the relative bioavailability of the formulations could be observed