Examination of the Rate and Extent of Drug Released from Commercial Topical Delivery Systems During Wear: An Example with Lidocaine Topical Systems.

OBJECTIVE: This study aimed to determine the extent and rate of lidocaine released in vivo from two bioequivalent topical delivery systems (TDS) by using complementary assessments: pharmacokinetic analysis in healthy human volunteers, and residual lidocaine in TDS following 12 h of wear. The goal was to explore a potentially more clinically meaningful strength presentation than percent active pharmaceutical ingredient loaded in topical systems. METHODS: A three-arm, open-label, crossover clinical study was conducted in 23 human subjects, with 5% lidocaine topical systems from two manufacturers, and intravenous lidocaine administration. Residual drug and LC-MS/MS analyses were performed on worn TDS and serum samples. The rate and extent of drug released from the TDS during wear were determined through (1) calculations of consumed lidocaine via analysis of residual drug in worn TDS, and (2) a pharmacokinetic approach via derivation of the absolute clearance and serum lidocaine concentration at steady state. RESULTS: Overall the pharmacokinetic approach underestimated the amount transferred to the subject and exhibited greater variability, which may relate to natural inter-subject variability in pharmacokinetic parameters. Further, lidocaine TDS are intended for localized, not systemic, delivery and this may also explain some of the variability seen in the systemic serum concentrations. CONCLUSIONS: The residual drug and pharmacokinetic approaches align well for transdermal formulations, but the differences in administration route (topical versus transdermal) all but eliminates the potential use of the pharmacokinetic approach unless additional compartmental modeling is explored.

Quantitative chromatographic method development for residual lidocaine in topical systems and biological samples.

Background: The aim of this work was to develop and validate sensitive and efficient analytical methods for estimating systemic drug exposure and residual drug following the application of topical delivery systems. Materials & methods: Lidocaine was extracted using a liquid-liquid extraction technique from commercial topical products and analyzed using ultra high-performance liquid chromatography. A separate LC-MS/MS method was developed for analyzing human serum samples. Results & conclusion: The developed methods were successfully applied for estimating lidocaine content in two commercial products demonstrating 97.4-104.0% for product A and 105.0-110.7% for product B. The LC-MS/MS method displayed successful analysis of lidocaine from human serum samples. The developed methods are recommended for quantifying systemic exposure and residual drug analysis of topical systems.

A forward to optimization of antivenom therapy: An in vivo study upon the effectiveness of the antivenom against early and delayed nephrotoxicity induced by the venom of the Iranian scorpion Hemiscorpius lepturus in rat.

The aim of the present in vivo study was to identify the optimal effective dose, the most favorable time and the route of administration of the available polyvalent scorpion antivenom against the toxic effects induced by Hemiscorpius lepturus (H. lepturus) venom in rat. The end point for assessment included measurement of alanin-amino-peptidase (AAP) and N-acetyl-b-d-glucosaminidase (NAG), biochemical urine analysis and histopathological assessment. The results showed that a single subcutaneous 50 µg of the venom produced significant increase in the AAP and NAG enzyme activity, urinary biochemical parameters and induced histopathological structural abnormalities in the renal system. The optimal effective co-administered dose of the antivenom was 0.5 ml, which when administered 1 and 2 h of envenomation by intravenous (IV) and subcutaneous (SC) routes respectively produced significant protection against these toxic effects. Prudently, the significance of these findings need to be assessed in further clinical studies.

The Role of Different Supplements in Expression Level of Monoclonal Antibody against Human CD20.

BACKGROUND: Recombinant monoclonal antibodies have been marketed in last three decades as the major therapeutic proteins against different cancers. However choosing a proper medium and supplements to reach the high expression is a challenging step. Despite of commercial serum free and chemically defined media, there are still numerous researches seeking the optimum media to gain higher expression titer. Selecting the best basal media followed by proper supplementation to increase the cell density and expression titer needs proper and accurate investigation. METHODS: In this study, we have determined the expression titer of monoclonal antibody against human CD20 using soy extract, Essential Amino Acid, Non-Essential Amino Acid, Panexin NTS, Peptone, Yeast extract, Insulin-transferrin selenite, Human Serum Albumin, Bovine Serum Albumin, Lipid, and two commercially available supplements, Power and Xtreme feed. In each experiment, the expression level was compared with a well defined media, ProCHO5, RPMI 1640 and DMEM-F12. RESULTS: It has been shown that supplementing the ProCHO5 basal medium with 10% power feed or combination of 5% PanexinNTS,1.5 g/L yeast and 1.5g/L peptone results in the best production levels with 450 and 425 mg/L of anti CD20 mAb expression level, respectively. CONCLUSION: Panexin NTS, yeast and peptone cane be proper supplement for fed-batch cell culture instead of commercial Power feed supplement which is a cost effective way to increase expression level. And thereby ProCHO5 may be replaced with common media such as RPMI 1640 and DMEM-F12.

Optimization of Ibuprofen Delivery through Rat Skin from Traditional and Novel Nanoemulsion Formulations.

The topical delivery of non-steroidal anti-inflammatory drugs (NSAIDS) such as Ibuprofen has been explored as a potential method of avoiding the first pass effects and the gastric irritation, which may occur when used orally. Ibuprofen is formulated into many topical preparations to reduce the adverse effects and simultaneously avoid the hepatic first-pass metabolism as well. However, it is difficult to obtain an effective concentration through topical delivery of Ibuprofen due to its low skin permeability. The aim of this study was to develop two types of nanoemulsions formulations and focused on the screening of Ibuprofen-loaded nanoemulsions and evaluating the influence of these types of nanoemulsions on the skin permeability of the drug. In both nanoemulsion formulations, oil was similar, but the surfactant and co-surfactant were different. The effect of independent variables on skin permeability parameters was evaluated using full factorial design. Results demonstrate that novel formulations were more effective as skin enhancer than traditional formulation. In case of the novel formulation, any increase in percentage of surfactant and co-surfactant had increasing effect on flux (Jss). On the other hand, the proportion of surfactant/co-surfactant (S/C) demonstrated reverse correlation with Jss. While, in traditional formulations, direct correlation was found between both variables, and Jss. Comparison between two types of nanoemulsion formulations revealed that, novel formulations were more effective as topical Ibuprofen carrier in contrast to traditional type due to lower amounts of surfactant and co-surfactant and less irritating effect.

The pattern of poisoning in southwestern region of iran: envenoming as the major cause.

BACKGROUND: An analysis performed on the collected data from the Local Drug and Poison Information Centre (DPIC) of Jundishapur University revealed that stings are the main causes of poisonings with frequency of 56%, followed by drug poisoning in 31%, and chemical exposure poisoning in 5.5% in Khuzestan, the southwestern province of Iran. OBJECTIVES: The aim of the present study was to report the prevalence of poisoning in Khuzestan province referred to hospitals during the year 2007, on the basis of documents from the local Drug and Poison Information Centre (DPIC) and the main Khuzestan Hospitals Discharge Registry, to elucidate demographic trends of poisoning in this region. MATERIALS AND METHODS: In the present study, 3258 cases of poisoning including 4.7% of all admissions to hospitals of Khuzestan during one year (2007) were investigated. Antidepressant drugs were the main-drug category inducing poisoning (24.37%). Others include sedative-hypnotics (19%), tricyclic antidepressants (TCA) (14.7%) and cardiovascular drugs (11.4%). RESULTS: The research showed that most poisonings are occurred in autumn (29.6%) season. Besides the high poisoning rate of envenoming by animals in Khuzestan province, it seems that the pattern of poisoning is different with other Iran and worldwide regions. CONCLUSIONS: This may raise the attention of health service policy makers in Iran to establish a more effective diagnosis, management and implementing health policy services.