Application of Graphene and its Derivatives in Cancer Diagnosis and Treatment.

Although chemotherapies are successful in some cases, systemic toxicity could be simultaneously observed due to the lack of drugs selectivity to cancerous tissues, leading to the failure of the chemotherapies. Furthermore, the therapeutic effects will be significantly improved if the anticancer drugs could be delivered to cancer cells with high selectivity. In recent years, there have been many advances in the field of diagnosis and treatment of cancer as a result of the development of novel materials with noticeable and often unique properties. Nanoparticles have unique biological properties, owing to their small size and large surface area-to-volume ratio, which allow them to bind, absorb, and carry compounds such as small molecule drugs, DNA, RNA, proteins, and probes with high efficiency. In the course of the last decade, Graphene and its derivatives have attracted growing interest in medicinal and pharmaceutical sciences, and many studies have focused on the potential of Graphene and its derivatives as carriers for targeted drug delivery intended for cancer diagnosis and therapies. In the present study, we will review the characteistics and application of Graphene and its different derivatives and finally discuss the opportunities, limitations, and challenges in this encouraging field.

Enhanced skin penetration of lidocaine through encapsulation into nanoethosomes and nanostructured lipid carriers: a comparative study.

Lipid based nanoparticles have become a major research object in topical drug delivery to enable drugs to pass the stratum corneum and reach the desired skin layer. The present investigation deals with the encapsulation of lidoacine into nanostructured lipid carriers (NLCs) and nanoethosomes for improving its dermal delivery and consequently local anesthetic efficacy. Concurrently these two topical delivery systems were compared. Lidocaine-loaded NLCs and nanoethosomes were characterized by various techniques and used for an in vitro skin penetration study using excised rat skin and Franz diffusion cells. The nanoparticles were tracked in the skin by following the Rhodamine-labled nanocarriers under fluorescent microscopy. Optimized lidocaine-loaded NLCs (size 96 nm, zeta potential -13.7 mV, encapsulation efficiency (EE) % 69.86% and loading capacity (LC) % 10.47%) and nanoethosomes (size 105.4 nm, zeta potential -33.6 mV, EE 40.14% and LC 8.02%) were chosen for a skin drug delivery study. Higher skin drug deposition of NLCs and nanoethosomal formulations compared to lidocaine hydroalcoholic solution represented a better localization of the drug in the skin. NLC formulation showed the lowest entered drug in the receptor phase of Franz diffusion cell in comparison with nanoethosomes and hydroalcoholic solution confirming the highest skin accumulation of drug. Both colloidal systems showed superiority over the drug solution for dermal delivery of lidocaine, however, NLC exhibited more promising characteristics than nanoethosomes regarding drug loading and skin targeted delivery.

Carrier free dry powder formulation of sildenafil for potential application in pulmonary arterial hypertension.

The present study was designed to prepare sildenafil carrier free dry powder inhalation (DPI) formulation for the treatment of idiopathic pulmonary arterial hypertension (IPAH). Sildenafil DPI formulations were fabricated by spray drying technique. The ideal formulation was optimized using different solvent type (methanol, dimethyformamide and water), concentration (5 and 50 mg/mL) and pH (2 and 7.4) of feed solution. Particles size distribution, morphology and crystallinity of fabricated microparticles were evaluated by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) methods, respectively. The aerosolization efficiency of formulations were assessed by next generation impactor equipped with an Aerolizer. Results indicated that evaluated variables had great impacts on powder characteristics which significantly influenced aerosolization performance of formulations. The aerosolized fraction of formulations was improved from 2 to 70% by changing in solvent type and drug concentration in spray dryer feeding solution. Aerosolization performance of powders were well correlated and interpreted by their morphologies as depicted from SEM images. DSC results also indicated that crystallinity of all formulations were reduced by spray drying procedure. Optimization of spray drying technique for production of Sildenafil carrier free DPI formulation in this study may pave a way for locally treatment of IPAH.

Investigation of the memory impairment in rats fed with oxidized-cholesterol-rich diet employing passive avoidance test.

BACKGROUND: Recent studies have shown that hypercholesterolemia, besides being a risk factor for cardiovascular diseases, has also toxic effects on central nervous system. The design of the present study was to investigate the effects of dietary cholesterol and oxidized cholesterol on cognitive function. METHODS: Male Wistar rats were randomly divided into 3 groups. The animals were fed with three normal, 2% cholesterol-rich, and 2% oxidized cholesterol-rich diets for 14 weeks. Memory impairment was analyzed by passive avoidance test. Coenzyme Q10 content was also measured by a validate RP-HPLC method. Besides, lipid peroxidation in serum and brain tissue was determined by malondialdehyde concentration measurement. RESULTS: The results showed that feeding rats with high oxidized cholesterol diet for 14 weeks significantly impaired the cognitive function compared to the normal (P<0.001) and high cholesterol-fed groups (P<0.01). The memory impairment was positively correlated to the serum level of the oxidized LDL; it was significantly associated with the increased malondialdehyde concentration on the brain tissue of both groups (P<0.05 and P<0.001, respectively). The total antioxidant level in the serum was also decreased in rats fed with the oxidized cholesterol (P<0.05). Moreover, the brain coenzyme Q10 content was significantly declined in the animals fed with the oxidized cholesterol-rich diet compared to the animals fed with the normal (P<0.01) and cholesterol-rich diets (P<0.05). CONCLUSION: The results suggested that the high dietary intake of the oxidized-cholesterol might impair the memory that could be correlated to the oxidative stress and declined the coenzyme Q10 content of the brain tissue.

Acute administration of pioglitazone attenuates morphine withdrawal syndrome in rat: a novel role of pioglitazone.

BACKGROUND: Long-term exposure to opiates such is morphine induces dependence. PURPOSE: The purpose of the present study was to investigate the effects of the acute administration of pioglitazone, a selective agonist of peroxisome proliferator activated receptors gamma (PPAR-γ), on the morphine withdrawal syndrome in the rat. METHODS: Male Wistar rats (200-250 g) were selected randomly and divided into 8 groups including 2 non-dependent groups and 6 morphine-dependent groups which were received additive doses of morphine subcutaneously at an interval of 12 h for 9 continuous days. On the ninth day, only the morning dose of morphine was injected and 2 h later, morphine withdrawal was precipitated by naloxone and then ten distinct withdrawal behaviors were recorded for 45 min. Pioglitazone (5, 10, 20 and 40 mg/kg) was gavaged 2 h before naloxone injection. It is worth noting that 1 h before the pioglitazone (40 mg/kg) gavage, GW-9662 (2 mg/kg), a selective PPAR-γ antagonist, was administrated in order to evaluate the possible role of the PPAR-γ. RESULT AND DISCUSSION: The results of this study showed that administration of pioglitazone (40 mg/kg) decreased all withdrawal signs and the statistical analysis indicated that pioglitazone could attenuate the total withdrawal scores significantly. Administration of GW-9662 had no significant effect on pioglitazone attenuation effect on morphine withdrawal symptoms.Taking together, it was concluded that acute oral administration of pioglitazone prevented naloxone-precipitated withdrawal symptoms and GW-9662 could not revert its effect on morphine withdrawal syndrome. It seems that pioglitazone suppresses morphine withdrawal syndrome through PPAR-γ independent mechanisms.

Dietary cholesterol and oxidised cholesterol: effects on sperm characteristics, antioxidant status and hormonal profile in rats.

Present study was designed to compare the potential effects of high serum levels of LDL and oxidised LDL (OxLDL) on spermatogenesis parameters in male Wistar rats. Animals were allocated into three groups and were fed for 14 weeks with normal, cholesterol-rich and oxidised cholesterol-rich diets. Blood lipid profile, sex hormones level, as well as sex organs weight were evaluated. The sex organs weight in oxidised cholesterol-fed group was significantly reduced (P < 0.05). Spermatozoa count in the group with high serum concentration of OxLDL (64 ± 4.2 × 10(6) ) was markedly lower (P < 0.01) than that of normal rats (87 ± 4.1 × 10(6) ) and rats with high serum level of LDL (90 ± 6.3 × 10(6) ). Similarly, the percentage of viable spermatozoa was significantly (P < 0.001) decreased from 78% to 52% by high level of OxLDL in serum. While, nonoxidised LDL did not have suppressive effects on spermatogenesis and organs weight. Consistent with these effects, the serum concentration of sex hormones including FSH (P < 0.001), LH (P < 0.001) and testosterone (P < 0.01) was significantly decreased only in rats with high level of OxLDL but not in rats with high level of nonoxidised LDL. In conclusion, high OxLDL level showed higher destructive effect on reproductive system compared to the high LDL level.

Effects of LDL and oxidized LDL on cardiac function in isoproterenol-induced myocardial infarction in rat.

Notable discussions have been developed over the distinctive effects of LDL and oxidized LDL (OxLDL) on myocardial functions. The aim of the present study was to investigate the effects of OxLDL on electrocardiogram and hemodynamic parameters of rat's heart in isoproterenol (ISO)-induced myocardial infarction (MI) model.Male Wistar rats were allocated in to 6 groups and receive one of the 3 formulated diets (standard, cholesterol-rich and oxidized cholesterol-rich diets). After 14 weeks to induce MI, rats in 3 groups were received ISO (100 mg/kg) for 2 consecutive days subcutaneously. Lipid profiles, electrocardiogram patterns and hemodynamic parameters of all groups were investigated.Serum levels of LDL, cholesterol and triglycerides were significantly higher in the fat-rich diet fed groups compared to control group (P<0.001). The ISO-treated rats showed a marked reduction in the R-amplitude, R-R interval, LVSP, left ventricular contractility (LVdP/dtmax) and relaxation (LVdP/dtmin) as well as severe elevation in ST-segment and LVEDP value compared to the respective normal rats. High serum level of OxLDL resulted in significant exacerbation in the destructive effects of ISO on R-amplitude, R-R interval, LVSP, left ventricular contractility (LVdP/dtmax), relaxation (LVdP/dtmin), ST-segment and LVEDP values. Additionally, heart to body weight ratio as an index of myocardial edematous was also increased significantly. However, changes in these parameters in rats fed with cholesterol-rich diet were not significant.Generally, results indicated that the effects of high OxLDL level on electrocardiogram and hemodynamic parameter after MI was more reliable than effects of high LDL level.

Duloxetine attenuated morphine withdrawal syndrome in the rat.

BACKGROUND: Long term exposure to morphine can induce dependence. The exact mechanisms of dependence are not yet fully understood. Many studies have been conducted to find new drugs that can prevent dependence. This study examined the effects of the chronic administration of duloxetine on the morphine withdrawal syndrome in rats. METHODS: To this end, male Wistar rats (170-220 g) were randomly divided into 5 groups including one saline treated group (non-depend­ent group) and 4 morphine dependent groups. The experimental groups received additive doses of morphine for 9 days in order to induce dependence according to the following protocol: day 1:5 mg/kg/12 h, days 2 and 3: 10 mg/kg/12 h, days 4, 5:15 mg/kg/12 h, days 6 and 7: 20 mg/kg/12 h and days 8 and 9: 25 mg/kg/12 h. On the ninth day, the morning dose of morphine was only injected. It is worth noting that 30 min before the morning dose of morphine, duloxetine (10, 20, and 40 mg/kg) was injected intraperitoneally. In addition, 2 h after the last injection of morphine, the morphine withdrawal was precipitated by naloxone. The withdrawal signs were recorded for 30 min; these signs included jumping, rearing, genital grooming, abdominal writhing, wet dog shaking, and teeth grinding. RESULTS: The results of the study revealed that the chronic administration of duloxetine decreased all the withdrawal signs. Besides, it attenuated the total withdrawal scores significantly. CONCLUSION: Results indicate that the regulatory effects on serotonergic and noradrenergic parameters might be associated with the amelioration of the withdrawal symptoms.

Drug release kinetic analysis and prediction of release data via polymer molecular weight in sustained release diltiazem matrices.

This study was conducted to investigate the effects of HPMC (K4M and K100M) as well as tragacanth on the drug release rate of diltiazem (DLTZ) from matrix tablets prepared by direct compression method.Mechanism of drug transport through the matrices was studied by fitting the release data to the 10 kinetic models. 3 model independent parameters; i. e., mean dissolution time (MDT), mean release rate (MRR) and release rate efficacy (RE) as well as 5 time point approaches were established to compare the dissolution profiles. To find correlation between fraction of drug released and polymer's molecular weight, dissolution data were fitted into two proposed equations.All polymers could sustain drug release up to 10 h. The release data were fitted best to Peppas and Higuchi square root kinetic models considering squared correlation coefficient and mean percent error (MPE). RE and MRR were decreased when polymer to drug ratio was increased. Conversely, t60% was increased with raising polymer /drug ratio. The fractions of drug released from the formulations prepared with tragacanth were more than those formulated using the same amount of HPMC K4M and HPMC K100M.Preparation of DLTZ matrices applying HPMCK4M, HPMC K100M and tragacanth could effectively extend the drug release.

Micro-suspension coating method: a new approach in formulation and development of controlled porosity osmotic pump systems.

PURPOSE: The aim of this study was to design and evaluate diltiazem hydrochloride controlled porosity osmotic pump (CPOP) system employing a new coating technique named the micro suspension coating method. METHOD: In this method the fast dissolving pore formers were suspended in polymeric coating solution as micronized particles. Cellulose acetate and dextrose were used as film former polymer and pore former, respectively. 4 comparative parameters i. e., D24h (cumulative release percent after 24 h), Devzero (mean percent deviation of drug release from zero order kinetic), tL (lag time of the drug release) and RSQzero were used to assess various formulations. RESULTS: The results showed a significant increase of D24h due to the decrease in the thickness of the semipermeable membrane (SPM) and increase of the sucrose concentration (P<0.05). An inverse relationship was seen between sucrose amounts and drug release lag times of the formulations. In addition, lag time was significantly reduced following addition of tween 80 to SPM formulation (P<0.05). Results of scanning electron microscopy studies exhibited formation of pores in the membrane from where the drug release occurred. CONCLUSION: Micro suspension coating method was found to be a novel and promising method to formulate CPOP system of diltiazem hydrochloride.

Reduction of coenzyme q10 content: a possible effect of isoproterenol on heart failure and myocardial infarction in rat.

Myocardial infarction (MI) was induced by subcutaneous injection of isoproterenol (ISO) to investigate the effect of ISO on Coenzyme Q10 (CoQ10) content of myocardium and subsequent effects on lipid peroxidation, electrocardiogram pattern and hemodynamic parameters of the rat's heart.36 male Wistar rats were divided randomly into 6 groups. To induce heart failure (HF) and MI, 10 and 100 mg/kg of ISO was administered subcutaneously for 10 and 2 consecutive days, respectively. The effects of ISO on myocardium CoQ10 content, concentration of malondialdehyde, ECG pattern and hemodynamic parameters of heart were analyzed.ISO-treated rats showed significant alteration in heart hemodynamic parameters such as reduction of left-ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, besides increase of left ventricular end-diastolic pressure. Significant depletion of heart CoQ10 content (from 4.57 and 4.55 µg/100 mg tissue in control groups to 2.85 and 2.89 µg/100 mg tissue in ISO-induced HF and MI groups respectively) and increase in tissue levels of malondialdehyde (47.1 and 53.8 nmol/100 mg tissue in ISO-induced HF and MI groups, respectively) were also observed in ISO-treated animals compared with the normal animals (17.4 and 18.8 nmol/100 mg tissue in control groups, respectively). Additionally CoQ10 improved ISO effects on hemodynamic parameters and ECG pattern in ISO-induced HF and myocardial injury.The present findings have demonstrated that the cardiotoxic effects of ISO such as oxidative damage and hemodynamic declination might be related to depletion of CoQ10 concentration.

CoQ10 and L-carnitine attenuate the effect of high LDL and oxidized LDL on spermatogenesis in male rats.

BACKGROUND: It is estimated that one-third of infertility cases are due to male factors. Hyper-cholesterolemia is a social problem in many developed countries and contributed with a heterogeneous group of disorders characterized by an excess of cholesterol and its derivatives in the blood stream. PURPOSE: The objective of the present study was to investigate the protective effects of coenzyme Q10 and L-Carnitine supplementation on semen parameters, sperm function and reproductive hormone profiles in male Wistar rats with high LDL and Oxidized LDL (OxLDL) blood levels. METHODS: Animals were fed with cholesterol and oxidized cholesterol-rich diets for 14 weeks to elevate the LDL and OxLDL blood level, respectively. Pretreatment with coenzyme Q10 (10 mg/kg/day, oral) and L-Carnitine (350 mg/kg/day, oral) were conducted for 5 consecutive weeks. Sex hormones levels, malondialdehyde and total antioxidant concentrations, as well as testis, epididymis and seminal vesicle weight were also analyzed. RESULTS: Following high LDL and OxLDL blood levels, decrease in the sperms count and viability, weights of testis, epididymis and seminal vesicle as well as concentration of testosterone and LH hormone were observed. On the other hand, in contrast to reduction of total antioxidant level, malondialdehyde concentration, both in serum and testis, was increased. However, pretreatment with L-carnitine and coenzyme Q10 increased serum sex hormones level and improved semen parameters significantly. CONCLUSION: Overall, pretreatment with coenzyme Q10 and L-Carnitine attenuated the destructive effects of high LDL and oxidized LDL levels on spermatogenesis parameters in male rats.

Effects of L-carnitine and coenzyme q10 on impaired spermatogenesis caused by isoproterenol in male rats.

Nowadays, cardiovascular diseases and male infertility are two big health problems in industrial countries.The aim of the present study was to investigate the protective role of coenzyme Q10 and L-Carnitine pretreatment in the impaired spermatogenesis caused by isoproterenol (ISO) in male rats.Thirty-two male Wistar rats were allocated in 4 groups. ISO was injected for 2 consecutive days (100 mg/kg) in ISO treated groups. Before ISO administration, pretreatment with Coenzyme Q10 (10 mg/kg/day) and L-Carnitine (350 mg/kg/day) were conducted for 20 consecutive days. Sex hormones level, malondialdehyde (MDA) and total antioxidant concentration as well as testis, epididymis and seminal vesicle weight were investigated.Increase in the concentration of MDA and decrease in total antioxidant level was observed following ISO administration. Accordingly, the sperm viability as well as testis, epididymis and seminal vesicle weights were decreased. In the case of sex hormones, the testosterone and LH levels were decreased and the concentration of FSH was increased. Pretreatment with L-carnitine and Coenzyme Q10 significantly decreased the MDA level and increased total antioxidant, LH and testosterone levels. Pretreatment with L-carnitine and Coenzyme Q10 also improved semen parameters and organs weight which were impaired by ISO administration.L-carnitine and Coenzyme Q10 pretreatment could protect spermatogenesis in male rats with ISO administration.

Preparation and In vitro Evaluation of Naproxen Suppositories.

The aim of this work was to develop the best formulations for naproxen suppositories. The effects of different bases and surfactants on the physicochemical characteristics of the suppositories were determined by several tests such as weight variation, melting point, assay, hardness, and release rate. All formulations met the standard criteria for tested physicochemical parameters; weight variation (97-112%), content uniformity (97-105%), melting point (4.66-8.7 min) and hardness tests (>5400 g). Based on release rate studies, hydrophilic, and lipophilic bases without surfactants were not suitable bases for naproxen suppository. Amongst the formulations containing surfactants only Witepsol H15 with 0.5% w/w of Tween 80 and Witepsol W35 with 0.5% of cetylpyridinium chloride were suitable and released nearly complete drug during 30 and 60 min, respectively. This study demonstrates the effects of incorporation of known agents on the in vitro release characteristics of naproxen suppository.

The effect of Beta-cyclodextrin on percutaneous absorption of commonly used Eusolex® sunscreens.

BACKGROUND: There is a serious concern about the topical and systemic absorption of organic ultraviolet filters in sunscreen formulations and subsequent phototoxic and photo allergic reactions. Ideally, a sunscreen should localize in the surface of stratum corneum and create a barrier against UV radiation, but not penetrate into the underlying viable tissues and systemic circulation. PURPOSE: The objective of the present study was to determine the effects of ß-cyclodextrin (ß-CDX) complexation on the transdermal penetration of 3 commonly used sun blocking agents, Eusolex ® 4360 (avobenzone), Eusolex ® 9020 (Oxybenzone) and Eusolex ® 232 (Ensulizole). METHODS: The complexation of the sunscreen agents with ß-CDX was performed by 3 methods and confirmed by differential scanning calorimetry (DSC). Sunscreens, and their physical mixtures and complexes with ß-CDX were introduced into a model cream base (o/w emulsion). To find out the influence of ß-CDX, sunscreen creams were applied to the rat skin in vitro in standard Franz diffusion cells and the amount of sunscreen permeated after 6 h was assessed by HPLC. RESULTS: The skin penetration flux of the UV filters was significantly reduced (4­15 fold) by complexation with ß-CDX. Complexation also could prolong absorption lag time of sun blocking agents to more than 150 min. CONCLUSION: Considering the ability of ß-CDX complexation in the reduction of flux and enhancement ratio as well as prolongation of absorption lag time, this technique could be very helpful for reducing systemic absorption of the UV filters and subsequent toxicity and allergic reaction.

Comparative bioequivalence study of two marketed formulation of betamethasone injectable suspensions.

BACKGROUND: The aim of this study was to determine the bioequivalence of generic (test) and branded (reference) formulations of betamethasone injectable suspension in healthy Iranian subjects for the purpose of meeting regulatory requirements for bioequivalence of the generic formulation in Iran. METHODS: 24 healthy Iranian male volunteers were participated for this single-dose, randomized, open label, 2 period crossover study separated by a 2-week washout period. For the assessment of betamethasone, blood samples were obtained before and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 h after drug administration. Plasma concentration of betamethasone was analyzed with a simple, rapid and validated high performance liquid chromatography method with ultraviolet detection. Pharmacokinetic parameters, representing the rate (Cmax, Tmax), and the extent (AUC0-t and AUC0-∞) of betamethasone absorption were calculated and analyzed for 2 formulations. The 2 formulations were to be considered bioequivalent if the 90% confidence intervals (CI)s for the logarithm-transformed values of Cmax, AUC0-t and AUC0-∞ fell within the predetermined range of 80-125%. RESULTS: The 90% CIs of Cmax, AUC0-t and AUC0-∞ were 85.4-104.4%, 96.2-112.1% and 98.3-115.8%, respectively. CONCLUSION: Based on the 90% CIs of Cmax, AUC0-t and AUC0-∞ in these healthy Iranian male subjects, the test and reference formulations of betamethasone injectable suspension met the regulatory requirements for bioequivalence.

Single dose bioequivalence study of two brands of olanzapine 10 mg tablets in Iranian healthy volunteers.

This single dose, randomized, open label, 2-period and crossover study in healthy Iranian adult volunteers was conducted to compare the bioavailability of 2 branded formulations of olanzapine 10 mg tablets. 24 volunteers received one tablet of each olanzapine 10 mg formulation. Drugs were administered after a 12 h overnight fast in each of 2 treatment days which separated by a 2-week washout period. Serial blood samples were collected over a period of 72 h. Plasma was analyzed using a validated high performance liquid chromatography method with ultraviolet detection in the range of 2-24 ng/mL with a lower limit of quantitation of 1.25 ng/mL. A non-compartmental method was employed to determine the pharmacokinetic properties (Cmax, Tmax, AUC0-t, AUC0-∞ and T1/2) to test to bioequivalence. Cmax, AUC0-t and AUC0-∞ were used to test the bioequivalence after log-transformation of plasma data. The mean (SD) Cmax, AUC0-t and AUC0-∞ for the test formulation were 15.82 (3.15) ng/mL, 447.19 (100.64) ng.h/L and 570.75 (130.55) ng.h/L respectively. Corresponding values for the test formulation were 15.72 (4.25) ng/mL, 440.37 (98.75) ng.h/mL and 558.66 (129.57) ng.h/mL. For test formulation vs. the reference formulation, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t and AUC0-∞ were 97.6-110.0%, 96.4-109.4% and 97.3-109.2%. In these volunteers, based on the FDA regulatory definition, results from the pharmacokinetic analysis suggested that the test and reference formulations of olanzapine 10 mg tablets were bioequivalent.

The effect of pore-formers and plasticizers on the release kinetic of diltiazem hydrochloride from the controlled porosity osmotic pumps.

BACKGROUND: The aim of this study was to design a controlled porosity osmotic pump (CPOP) tablet of diltiazem hydrochloride (DLTZ) to deliver the drug according to the zero order kinetic model over 24 h. METHOD: CPOPS were prepared by incorporating DLTZ in the tablet core followed by coating with cellulose acetate solution containing various types of pore-formers (PVP, PEG 2000, PEG 6000 and PEG 20000) and plasticizers (glycerol, castor oil and diethylphthalate). In vitro release study was conducted for the prepared formulations and the dissolution profiles were compared throughout four parameters, namely, D24 h (cumulative release in 24 h), tL (lag time), RSQzero (squared correlation coefficient of zero order kinetic) and MPDzero (mean percent deviation from zero order equation). RESULTS: Scanning electron microscopy showed formation of the pores in the semi-permeable membrane after coming in contact with dissolution medium. All formulations released more than 76% of contained drug during 24 h. CONCLUSION: Drug release rate and lag time were found to be directly proportional to the type and concentration of pore-formers as well as hydrophilicity of plasticizers. Our findings indicated that by optimizing formulation variables, CPOP tablets obeying zero order drug release kinetic could be obtained.

Preparation and evaluation of sustained release calcium alginate beads and matrix tablets of acetazolamide.

The aim of this study was to develop sustained release dosage forms of acetazolamide (ACZ) preparing its calcium alginate beads and matrix tablets. ACZ was incorporated into calcium alginate beads using microencapsulation method. Two methods were applied to prolong ACZ release rate. In the first method, the drug was incorporated into calcium alginate beads either alone or with various polymers in internal phase. The second method involved the preparation of matrix tablet from the beads benefiting direct compression method with or without various polymers in external phase. The release rate of these prepared formulations and an innovator's sustained-release capsule (Diamox®) were assessed. In-vitro dissolution studies revealed that the matrix tablets prepared by the second method containing NaCMC could sustain ACZ release properly and the drug released until 9 h. It was also found that several parameters such as concentration of sodium alginate, calcium chloride and ACZ; type and concentration of polymers; syringe needle size as well as distance between needle tip and surface of the calcium chloride could affect the properties of beads, matrix tablets and subsequently release profile. Preparation of polymer free beads, incorporation of polymers in internal phase of the beads and direct compression of the beads did not give sustained release property. Whereas, incorporation of NaCMC in the external phase of the beads in matrix tablets or in combination with alginate powder in directly compressed conventional tablets could produce dosage form with sustained release property similar to reference formulation.

Pharmacokinetics and bioequivalence evaluation of two brands of ciprofloxacin 500 mg tablets in Iranian healthy volunteers.

In the present study pharmacokinetics and bioequivalence of 2 brands of ciprofloxacin 500 mg were evaluated in 24 healthy male volunteers after a single dose oral administration in an open, randomized, 2-way crossover study.Blood samples were taken before and within 12 h after the administration of the drug. Plasma concentrations of ciprofloxacin were determined by a simple HPLC method with ultraviolet detection. The used method was validated for specificity, accuracy, precision and sensitivity. The mobile phase consisted of 0.025 M phosphoric acid, acetonitrile, and triethylamine. Analytical column was 5 µm Eurosphere C8 with a Eurosphere C8 guard column. The detector wavelength was set at 278 nm and the retention time was 10 min. The pharmacokinetic parameters, including peak plasma concentrations and time needed to reach the peak were obtained directly from plasma concentration-time profiles. The area under the curve was calculated using non-compartmental methods.The Cmax of 1476.8±319.9 ng/mL and 1 423.0±278.4 ng/mL were attained in about 1.67 and 1.58 h for test and reference formulations, respectively. The mean±SD values for AUC0-∞ were 9 665.3±2 880.2 and 9 716.1±2 572.1 ng.hr/mL for test and reference formulations, respectively. The pharmacokinetics parameters AUC0-t, AUC0-∞ and Cmax were calculated for bioequivalence after log-transformation of data. The 90% confidence intervals of test/reference for AUC0-t, AUC0-∞ and Cmax were (95.6-109.9%), (91.8-106.3%) and (95.2-112.8%), respectively and all were within the bioequivalence acceptance range of 80-125%.These results indicate that 2 tested formulations are bioequivalent and thus could be prescribed interchangeably.