• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.471-481
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• 2005

In Korea, generic drug and bioequivalence test are the hot issues since a new medical system of separation of dispensary from medical practice was started in 2000. The KFDA(Korea FDA) had revised several times ${\ulcorner}Guidance\;for\;bioequivalence\;test{\lrcorner}$. In vitro dissolution test has been extensively used as a quality control tool for solid oral dosage forms. In an effort to minimize unnecessary human testing, in vitro/in vivo correlations (IVIVC) between in vitro dissolution and in vivo bioavailability are increasingly becoming an integral part on extended release drug product development. The recently published US guidance, ${\ulcorner}Extended\;release\;oral\;dosage\;forms\;:\;development,\;evaluation,\;and\;application\;of\;in\;vitro/in\;vivo\;correlations{\lrcorner}$ will be helpful for us to make our own guideline.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.363-369
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• 2006

Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although this drug is commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liquid chromatography method with mass spectrometric detection(LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. This method has been validated for concentrations ranging from 5 to 1000 ng/ml with simple treatment. This technique has high level reproducibility, accuracy, and sensitivity. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. This study was aimed to investigate the feasibility of nasal delivery of granisetron for the elimination of vomiting. The effects of osmolarity, dosage volume at the same dose and applied dose on the nasal absorption of granisetron in rats were observed. No significant difference in the effect of osmolarity and dosage volume at the same dose was observed. As the applied dose of granisetron in nasal formulation increased, the absorption increased linearly. Based on these results it appears that only the applied dose(drug mass) determines the nasal absorption of granisetron. The bioavailability of granisetron on nasal administration of 4 mg/kg appeared to be comparable to that of intravenous administration of the same dose. These results suggest that granisetron can be efficiently delivered nasally and the development of nasal formulation will be feasible.

• Toxicological Research
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• v.13 no.4
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• pp.449-460
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• 1997

Single and 4 weeks oral administration of l-muscone, a major active ingredient of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs(3 males and 3 females) in acute experiments were administered orally with single dosage of 2,000 mg/kg and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of l-muscone, 0.2 mg/kg/day(low dosage group), 2 mg/kg/day(middle dosage group), or 20 mg/kg/day(high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korean Food and Drug Administration(1996.4.16). $LD_{50}$ value for beagle dogs was more than 2,000 mg/kg on oral route for both male and females. In animals administered with l-muscone, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, eye examination, hematology, serum chemistry, organ weight and other findings. No histolopathological lesions were observed in both control and treatment groups. Above data strongly suggest that l-muscone in beagle dogs is considered to be safe.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.229-254
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• 2004

The objective of this study was to scrutinize the rationale of SUPAC-MR and its application in processing postapproval changes to modified release solid oral dosage forms. The types of postapproval changes that were primarily covered with SUPAC-MR included variations in the components and composition, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. SUPAC-MR defined levels of postapproval changes that the industry might make. Classification of such categories was based on the likelihood of risk occurrence and potential impact of changes upon the safety and efficacy of approved drug products. In most cases, the changes could be classified into 3 levels. It described what chemistry, manufacturing, and control tests should be conducted for each change level. The important tests specified in SUPAC-MR were batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. It then suggested what type of a filing report should be submitted to the FDA for each change level. In general, level 1 changes could be reported in an annual report, whereas level 2 and/or 3 changes could be submitted in changes-being-effected or prior approval supplements. It could be understood that the purpose of SUPAC-MR was to maintain the safety and quality of approved modified release solid oral dosage forms undergoing certain changes. At the same time, it contributed to providing a less burdensome regulatory process with the manufacturers when they wanted to make postapproval changes. European regulatory agencies also implemented SUPAC-like regulations in handling such changes to drug products. Therefore, in this study a recommendation was made for KFDA and the Korean industry to evaluate thoroughly the usefulness of these guidances and regulations in dealing with postapproval changes to modified release solid oral dosage forms.

• The Korea Journal of Herbology
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• v.36 no.1
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• pp.51-57
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• 2021

Objects : In this study, I aimed to determine the size and administration Method of pills preparation in Treatise on Cold Damage Diseases. Methods : I investigated the Treatise on Cold Damage Diseases, Newly Revised Materia Medica, Variorum of the Classic of Materia Medica, The Korean Herbal Pharmacopoeia, and recent studies. Results : There were four kinds of pills preparation. Each size of pill preparation was equal to the Odongja, Tanwhan, Yolk, and quarter of daily dosage of Decoction. One pill of Tanwhan was equivalent to 16 pills of Odongja, and one Yolk was equal to 40 pills of Odongja. The Diameter of Odongja was 6.5 mm, Tanwhan was 16.37897 mm, and Yolk was 22.11484 mm. Jeodangwhan was equal to one quarter daily dosage of Jeodangtang. Maximum size to swallow with water was Odongja and daily dosage, which was 16 pills, includes one square-inch-spoon of powder preparation. When we made the pill preparation, it is difficult to make 16 pills using one square-inch-spoon of powder. Therefore, Zhang Zhongjing made one dosage started from 10 pills to 20 pills to find out optimum dose. Due to the difficulty of making precise size of pills and considerable amount of daily dosage, there was no smaller size than Odongja. When the size of Pill preparation was larger than Odongja, it was ground or boiled slightly to make suspensions. Conclusions : These results suggest that the sizes of Pill preparation in the Treatise on Cold Damage Diseases were true compared with reality.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.403-411
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• 2007

The importance of pharmaceutical additives is increasing and the sorts and application categories are being classified in detail. International pharmaceutical council based on IPEC-America, IPEC-Europe and JPEC was established for specifications, safety and efficacy, approval regulations of pharmaceutical additives in 1992. Therefore, scrutinized examination of pharmaceutical additives used for already approved domestic drug was performed under the supervision of KFDA and nomenclature on application categories of pharmaceutical additives was summarized and endowed their glossary. Additionally, the boundaries of pharmaceutical additives according to the dosage forms based on the principle of the dosage forms of Korean pharmacopoeia were classified. These informations could be available for standards & experimental methods, approval, evaluation, audit of drug and contribution for national welfare.

• Toxicological Research
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• v.14 no.2
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• pp.249-260
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• 1998

Single and 4 weeks oral administration of New Woohwangchungsimwon (NWCH) which was used l-muscone as substitutive material of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs(3 males and 3 females) in acute experiments were administered orally with single dose of 2,000 mg/kg and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of NWCH, 160 mg/kg/day (low dosage group), 400 mg/kg/day (middle dosage group), 1,000 mg/kg/day (high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korea Food and Drug Administration (1996. 4. 16). $LD_{50}$/ value for beagle dogs was more than 2,000 mg/kg per oral for both male and fe-males. In animals administered with NWCH, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical sign, urinalysis, eye examination, hematology, serum chemistry, organ weight and other fingings. No histological lesions were observed in both control and treatment groups. Above data strongly suggset that NWCH in beagle dogs is considered to be safe.

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.113-118
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• 2010

Pharmaceutical technology has primarily focused on the development of the best dosage forms depending on the route of administration. The design of dosage forms is greatly influenced by the route of administration. Due to a variety of advantages such as avoidance of first-pass effect, abundant blood supply and easy access to the absorption site, the oral cavity has frequently been selected as a site for drug delivery. Since the oral cavity is relatively unique from the anatomical and physiological viewpoint, one should always consider these conditions when designing the drug delivery systems for the oral cavity. In this regard, the current review paper was prepared to summarize the essential features of the drug delivery systems utilized in the oral cavity, along with the introduction of various dosage forms developed to date.

• Journal of Pharmacopuncture
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• v.12 no.4
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• pp.5-32
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• 2009

Objectives: This study was performed to analyse single dose toxicity of pure melittin(Sweet Bee Venom-Sweet BV) extracted from the bee venom by utilizing protein isolation method of gel filtration. Methods: All experiments were conducted at Biotoxtech, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP). Six weeks old female Sprague-Dawley rats were chosen for the pilot study and determined 30㎎/㎏ which is 4285 times higher than the clinical application dosage as the high dosage, followed by 15 and 7.5㎎/㎏ as mid and lose dosage, respectively. Equal amount of excipient to the Sweet BV experiment groups was administered as the control group. Results: 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all groups, and higher occurrence in the higher dosage groups. Hyperemia and movement disorder diminished with elapsed time. 3. For the weight measurement, male groups showed larger reduction in weight in accordance with higher dosage. Female groups didn't s how significant changes. 4. To verify abnormalities of organs and tissues, cerebellum, cerebrum, liver, lung, kidney, and spinal nerves were removed and conducted histological observation with H-E staining. No abnormalities were detected in any of organs and tissues. 5. One female rat in the 30㎎/㎏ group had amputated toe near the administered area and histopathological finding was hemorrhage with inflammation. This is presumed as a secondary infection after the administration of Sweet BV. Conclusion: Above findings suggest Sweet BV is relatively s safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.2
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• pp.117-128
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• 2022

Background: Moderate sedation is an integral part of dental care delivery. Target-controlled infusion (TCI) has the potential to improve patient safety and outcome. We compared the effects of using TCI to administer remifentanil/manual bolus midazolam with manual bolus fentanyl/midazolam administration on patient safety parameters, drug administration times, and patient recovery times. Methods: In this retrospective chart review, records of patients who underwent moderate intravenous sedation over 12 months in a private dental clinic were assessed. Patient indicators (pre-, intra-, and post-procedure noninvasive systolic and diastolic blood pressure, respiration, and heart rate) were compared using independent t-test analysis. Patient recovery time, procedure length, and midazolam dosage required were also compared between the two groups. Results: Eighty-five patient charts were included in the final analysis: 47 received TCI-remifentanil/midazolam sedation, and 38 received manual fentanyl/midazolam sedation. Among the physiological parameters, diastolic blood pressure showed slightly higher changes in the fentanyl group (P = 0.049), respiratory rate changes showed higher changes in the fentanyl group (P = 0.032), and the average EtCO₂ was slightly higher in the remifentanil group (P = 0.041). There was no significant difference in the minimum SpO₂ levels and average procedure length between the fentanyl and remifentanil TCI pump groups (P > 0.05). However, a significant difference was observed in the time required for discharge from the chair (P = 0.048), indicating that patients who received remifentanil required less time for discharge from the chair than those who received fentanyl. The dosage of midazolam used in the fentanyl group was 0.487 mg more than that in the remifentanil group; however, the difference was not significant (P > 0.05). Conclusion: The combination of TCI administered remifentanil combined with manual administered midazolam has the potential to shorten the recovery time and reduce respiration rate changes when compared to manual administration of fentanyl/midazolam. This is possibly due to either the lower midazolam dosage required with TCI remifentanil administration or achieving a stable, steady-state low dose remifentanil concentration for the duration of the procedure.