Mi-Kyeong Yoon

Formulation of microemulsion systems for transdermal delivery of aceclofenac.

An O/W microemulsion system was developed to enhance the skin permeability of aceclofenac. Of the oils studied, Labrafil® M 1944 CS was chosen as the oil phase of the microemulson, as it showed a good solubilizing capacity. Pseudo-ternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, Cremophor® ELP, and co-surfactant, ethanol, for micoemulsion formation. Eight different formulations with various values of oil of 6–30%, water of 0–80%, and the mixture of surfactant and co-surfactant (at the ratio of 2) of 14–70%. Thein vitro transdermal permeability of aceclofenac from the microemulsions was evaluated using Franz diffusion cells mounted with rat skin. The level of aceclofenac permeated was analyzed by HPLC and the droplet size of the microemulsions was characterized using a Zetasizer Nano-ZS. Terpenes were added to the microemulsions at a level of 5%, and their effects on the skin permeation of aceclofenac were investigated. The mean diameters of the microemulsions ranged between approximately 10≈100 nm, and the skin permeability of the aceclofenac incorporated into the microemulsion systems was 5-fold higher than that of the ethanol vehicle. Of the various terpenes added, limonene had the best enhancing ability. These results indicate that the microemulsion system studied is a promising tool for the percutaneous delivery of aceclofenac.

Kinetic characterization of swelling of liquid crystalline phases of glyceryl monooleate

Research in this paper focuses on the kinetic evaluation of swelling of the liquid crystalline phases of glyceryl monooleate (GMO). Swelling of the lamellar and cubic liquid crystalline phases of GMO was studied using twoIn vitro methods, a total immersion method and a Franz cell method. The swelling of the lamellar phase and GMO having 0 %w/w initial water content was temperature dependent. The swelling ratio was greater at 20°C than 37°C. The water uptake increased dramatically with decreasing initial water content of the liquid crystalline phases. The swelling rates obtained using the Franz cell method with a moist nylon membrane to mimic buccal drug delivery situation were slower than the total immersion method. The swelling was studied by employing first-order and second-order swelling kinetics. The swelling of the liquid crystalline phases of GMO could be described by second-order swelling kinetics. The initial stage of the swelling (t < 4 h) followed the square root of time relationship, indicating that this model is also suitable for describing the water uptake by the liquid crystalline matrices. These results obtained from the current study demonstrate that the swelling strongly depends on temperature, the initial water content of the liquid crystalline phases and the methodology employed for measuring the swelling of GMO.

Statistical Interpretation of Bioequivalence in 2 × 2 Crossover Design with Missing Observations

Statistical interpretations in a bioequivalence trial are considered and studied when the missing observations occurred in crossover experiment. Patel (1985) suggested the approximate test procedures for carryover effect and drug effect in crossover design when some of data are missing in the second period. A modified Patel method is newly proposed to the bioequivalence trial and it is compared with the current method through the simulation study.

Improved Antigen Delivery Systems with PLGA Microsphere for a Single-Step Immunization

A promising approach to the development of a new single-step vaccine, which would eliminate the requirement for multiple injections, involves the encapsulation of antigens into microspheres. Biodegradable poly(lactide-co-glycolide) (PLGA) microspheres gave us a bright insight for controling antigen release in a pulsatile fashion, thereby mimicking two or tree boosting injections. However, in spite of the above merits, the level of immunization induced by a single-shot vaccination is often lower tan two doses of alum-adsorbed antigen. Therefore, optima modification of the microsphere is essential for the development of single-step vaccines. In the review, we discuss the stability of antigen in microsphere, safety and non-toxic in human and encapsulation technology. Also, we attempted to outline relevant physicochemical properties on the immunogenicity of microsphere vaccine and attainment of pulsatile release pater by combination of different microsphere, as well as to analyze immunological data associated with antigen delivery by microsphere. Although a lot of variables are related to the optimized microsphere formulation, we could conclude that judicious choice of proper polymer type, adjustment of particles size, and appropriate immunization protocol along with a suitable adjuvant might be a crucial factor for the generation of long-lasting immune response from a single-step vaccine formulation employing PLGA microsphere.

Oral Bioavailability of Levosulpiride in Korean Healthy Male Volunteers

Pharmacokinetics and oral bioavailability of levosulpiride was determined in Korean healthy male volunteers. Thirty subjects received a single oral dose (25 mg) of a tablet in a randomized cross-over design. The plasma concentrations of levosulpiride were measured by HPLC and compared with those reported in the literature. Pharmacokinetic parameters for tablet (levosulpiride 25 mg) were revealed as follows: . The rate constant of the absorption phase was obtained based on the first-order kinetics. In the aspect of bioavailability, tablet was bioequivalent to the other product available in the Korea market. Intersubject variations and race differences were show in comparison with the published data in the literature, even though there was a linear relationship between dose ad extent of bioavailability.

Bioequivalence of Nimegen TM Soft Capsule to RoAccutane ® Soft Capsule (Isotretinoin 10 mg)

A bioequivalence study of soft capsule (Medica Korea Pharma. Co., Ltd.) to soft capsule (Roche Korea Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Thirty healthy male Korean volunteers received each medicine at the isotretinoin dose of 60 mg in a crossover study. There was one week wash-out period between the doses. Plasma concentrations of isotretinoin were monitored by a high performance liquid chromatography (HPLC) for over a period of 48 hours after drug administration. (the area under the plasma concentration-time curve from time zero to 48 hr) was calculated by the linear trapezoidal rule method. (maximum plasma drug concentration) and (time to reach ) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed . No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the ratio and the ratio for were , respectively. These values were within the acceptable bioequivalence intervals of . Thus, our study demonstrated the bioequivalence of with respect to the rate and extent of absorption.

Ex Vivo Permeability Characteristics of Porcine Buccal Mucosa to Drugs with Various Polarity

The aim of this study was to analyze characteristics of the barrier function of excised porcine buccal mucosa to the test compounds, estradiol, propranolol HCI, melatonin, and mannitol with a wide range of partition coefficient values. The permeability of melatonin was measured through frozen, stored, and fresh porcine buccal mucosa to examine the impact of storage conditions on the permeability of porcine buccal mucosa. The results demonstrated that the ex vivo permeability of the porcine buccal mucosa was greater for more lipophilic solutes, which was consistent with a series of molecules transported by passive transepithelial diffusion. The melatonin permeation profiles through frozen, stored, and fresh mucosa illustrated that damage was incurred by the freezing process of the mucosal tissue, leading to loss of the barrier function and thereby an increased permeation coefficient. It can be observed that the influence of compound lipophilicity on the association of the compounds with buccal mucosa was clear. The relationship between permeation coefficient and Log P values for the four compounds investigated demonstrated a proportional relationship, further confirming the importance of the lipophilicity of a compound to permeate the buccal mucosa. These results showed that the ex vivo porcine buccal mucosa model is a suitable tool to screen oral mucosal permeability.

Bioequivalence of Neuracetam Tablet to Neuromed Tablet (Oxiracetam 800 mg)

The purpose of the present study was designed to evaluate the bioequivalence of two oxiracetam tablets, Neuromed tablet (Korea Drug Co., reference drug) and Neuracetam tablet (Sam Jin Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Release of oxiracetam from the tablet in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty-four healthy volunteers, year in age and kg in body weight, were divided into two groups and a randomized cross-over study was performed. After oral administration of a tablet containing 800 mg of oxiracetam, blood samples were taken at predetermined time intervals and concentrations of oxiracetam in plasma were determined using HPLC-MS-MS. The dissolution profiles of two formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as , and were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed and untransformed . The results showed that the differences between two formulations based on the reference drug were 0.42%, 0.45% and -12.58% for , and , respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., and for , and , respectively), indicating that Neuracetam tablet is bioequivalent to Neuromed tablet. The major pharmacokinetic parameters, , and met the criteria set by KFDA for bioequivalence indicating that Neuracetam tablet is bioequivalent to Neuromed tablet.

Bioequivalence of Tagamet Tablet to Sinil CIMETIDINE Tablet (cimetidine 400 mg)

Cimetidine is a histamine antagonist, used for the treatment of endoscopically or radiographically comfirmed duodenal ulcer, pathologic GI hypersecretory conditions, and active, benign and gastric ulcer. Simple method for determining cimetidine in human plasma has been developed and validated. The analytical procedure for cimetidine showed a linear relationship in the concentration ranges from . Coefficient of variance (CV, %) for intraday and interday validation and relative error (RE, %) were less than . Based on this analytical method, the bioequivalence of two cimetidine 400 mg tablets, reference (Tagamet 400 mg) and test drug (Sinil CIMETIDINE 400 mg) was evaluated according to the guidelines set by the Korea Food and Drug Administration (KFDA). Release of cimetidine from the tablets in vitro was tested using KP VIII Apparatus II with various dissolution media (pH 1.2, 4.0, 6.8 buffer solutions and water). Twenty-four healthy volunteers, years in age and in body weight, were divided into two groups and a randomized cross-over study was performed. After oral administration of a tablet containing 400 mg of cimetidine, blood samples were taken at predetermined time intervals and concentrations of cimetidine in plasma were determined using HPLC equipped with UV detector. The dissolution profiles of the two tablet formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as and were calculated and ANOVA was employed for the statistical analysis of parameters. The results were revealed that the differences in and between the two tablets were 4.17 % and 0.97% respectively. At 90% confidence intervals, the differences in these parameters were also within . All of the above mentioned parameters have met the criteria of KFDA guidelines for bioequivalence, indicating that the test drug tablet (Sinil CIMETIDINE tablet) is bioequivalent to Tagamet 400 mg tablet.