• Journal of Pharmaceutical Investigation
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• v.34 no.1
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• pp.57-71
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• 2004

The objective of this study was to provide a better understanding of SUPAC-IR and its application in handling postapproval changes to immediate release solid oral dosage forms. Originally, SUPAC-IR was aimed at reducing the regulator burdern of the industry when they were making postapproval changes, but still at maintaining the formulation quality and performance of a drug product. The postapproval changes that were covered under SUPAC-IR included variations in the components ad composition of formulation, the site of manufacturing, batch size, manufacturing equipment, and manufacturing process. The guidance defined levels of changes, based on the likelihood of risk ocurrence and potential impact of postapproval changes upon the safety and efficacy of a drug product I suggested what a type of fing report should be submitted to the FDA for each level of change. Chemist, manufacturing, and control tests to be executed were also recommended for each change level The important tests specified in the guidance included batch release, stability, in vitro dissolution, and in vivo bioequivalence tests. However, there have been strong demands on revising the current SUPAC-IR in order to resolve some issues and to improve its usefulness in evaluating postapproval changes to immediate release solid oral dosage forms. In particular, the rigorous requirement of case C dissolution test and the definition of batch size were challenged by both academia and the industry. A revision work was in progress to reflect these inputs and to expand the utility of SUPAC-IR. As a result of these concerted efforts, an updated 2nd version of SPAC-IR would be likely to be issued ver soon to the public.

• Bulletin of the Korean Chemical Society
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• v.35 no.2
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• pp.557-561
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• 2014

The aim of the present study was to improve dosing of lacosamide, a functionalized amino acid used as an antiepileptic agent, from twice daily to once daily for the convenience of patients. A sustained-release lacosamide tablet was developed and dissolution testing was employed to determine in vitro release behavior using water or buffer solutions at pH 1.2, 4.0, or 6.8. Lacosamide was released for 12 h from the sustainedrelease (SR) tablet, as compared to complete release within 1 h from an immediate-release $Vimpat^{(R)}$ tablet. Each formulation (100 mg) was orally administered to six beagle dogs and six mini-pigs under fasted conditions, and pharmacokinetic parameters such as the area under the concentration time curve ($AUC_t$), the maximum plasma concentration ($C_{max}$), and the time at which this occurred ($T_{max}$) were calculated. These results showed similar values for $AUC_t$, $C_{max}$, and $T_{max}$ following oral administration of immediate-release ($Vimpat^{(R)}$) and SR lacosamide tablets.

• Korean Journal of Biological Psychiatry
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• v.16 no.4
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• pp.266-270
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• 2009

Adverse drug reactions are very common in clinical practice, and skin is one of the most frequent organs for adverse drug reactions. We report a case of a 71-year-old male patient who developed skin eruptions after switching formulation of quetiapine immediate release(IR) to quetiapine extended release(XR). He had been taking quetiapine IR(400mg/day) for treatment of manic episode which was developed one year ago. The patient showed great improvement of symptoms after taking quetiapine IR for about one year, thus dosage of medication was reduced to 50mg/day on the average. Unfortunately dose reduction has tended to worsen symptoms, so dose of quetiapine was increased again to 200mg/day with formulation changes to XR. Two days after he took new formulation, erythematous papules were occurred over his anterior neck and ventral side of left wrist. As he stopped quetiapine XR, the skin lesions gradually subsided. And he was successfully treated with readministration of quetiapine IR without any skin lesions.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.18 no.1
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• pp.506-512
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• 2017

The purpose of this study was to improve release rate and bioavailability of nateglinide formulation. Polymorphism selection and particle size control were performed to enhance formulation dissolution rate, and a pH modifier was included in the formulation to overcome pH-dependent solubility of nateglinide. The enhanced dissolution rate was characterized by using a dissolution test. The results showed that H-type raw material had a higher dissolution rate than that of B-type raw material. There was 6.2% difference in dissolution between the two materials at 60 min. With regard to particle size, raw material with a $1.13{\mu}m$ particle size showed a 20% faster release rate than that of raw material with a $2.28{\mu}m$ particle size. Furthermore, fumaric acid was included in formulation as a pH modifier. That addition produced a greater than 50% improvement in dissolution rate. In conclusion, dissolution rate of nateglinide can be enhanced by optimizing its polymorphism and particle size; moreover, a synergistic effect on the enhancement of dissolution rate is obtained by including fumaric acid, a pH modifier, in the formulation.

• Bulletin of the Korean Chemical Society
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• v.32 no.5
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• pp.1587-1592
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• 2011

The aim of the present study was to improve the solubility and bioavailability of a poorly water-soluble drug in human body, using a solid dispersion technique (hot melt extrusion). The solid dispersion was prepared by cooling the hot melt of the drug in the carrier (Vitamin E TPGS and PVP). The dissolution rate of formulation 1 from a novel formulation prepared by solid dispersion technique was equal to release of formulation 6 (40% of eprosartan mesylate is in contrast to teveten$^{(R)}$) within 60 min (Table 1). The oral bioavailability of new eprosartan mesylate tablet having vitamin E TPGS and PVP K29 was tested on rats and dogs. Of the absorption enhancer and polymer tested, vitamin E TPGS and PVP K29, resulted in the greatest increases of AUC in animals (about 2.5-fold increase in rat and dog). When eprosartan mesylate was mixed with the absorption enhancer and polymer in a ratio of 2.94:2:1, vitamin E TPGS and PVP K29 improved eprosartan mesylate bioavailability significantly compared with the conventional immediate release (IR) tablet Teveten$^{(R)}$ (formulation 7). These results show that solid dispersion using vitamin E TPGS and PVP K29 is a promising approach for developing eprosartan mesylate drug products.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.977-982
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• 2005

The aim of this study was to compare two formulations of film-coated pellets containing c1arithromycin after single oral dose study in healthy male volunteers. Two formulations with different coating polymers were prepared: formulation-1 (F-1) was prepared by incorporating three kinds of pH-dependent gradient-release coated pellets into capsules and formulation-2 (F-2) was prepared by coated with an insoluble semiosmotic film. Release profiles of filmcoated pellets were evaluated using paddle method under different conditions. Pharmacokinetic profiles of these formulations were obtained in three healthy male volunteers and compared to commercially available immediate release (IR) tablets. The relative bioavailability based on the $AUC_{0-24h}$ was found to be $96.2\%\;and\;58.7\%$ for F-1 and F-2 compared with IR, and the $T_{max}$ was delayed.

• Journal of Life Science
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• v.33 no.3
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• pp.268-276
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• 2023

This study was conducted to optimize the formulation conditions of the immediate-release layer of carvedilol in the development of a two-layer tablet formulation for carvedilol and ivabradine. Using a 2⁴+3 full-factorial design of experiments, excipients (microcrystalline cellulose, citric acid, and crospovidone) of the carvedilol immediate-release layer (wet granulation part) and process parameters for the tablet compression process (main compression) were optimized, and seven types of each dependent variable (assay, content uniformity, hardness, friability, disintegration, and dissolution [pH 1.2 and 6.8]) were evaluated using design expert software. The analysis of variance results confirmed that the main compression has a significant effect on hardness, friability, and disintegration time and that microcrystalline cellulose has a major effect on friability and dissolution. In addition, it was confirmed that citric acid has a significant effect on friability. Crospovidone affects friability and dissolution. According to the design space from the design of the experiment results, the optimized range is microcrystalline cellulose (~18.0-32.0 mg), citric acid (~0.5-12 mg), and main compression (~615-837 kgf). Consequently, this study confirmed the availability of manufacturing the carvedilol immediate-release layer in which all risk factors evaluated in the initial risk assessment are removed.

• Journal of Pharmaceutical Investigation
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• v.35 no.3
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• pp.157-163
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• 2005

The pellets with multiple drug release system (MDRS) of Diltiazem. HCl which consist of immediate drug release layer, drug reservoir layer and controlled release rate membrane, were prepared by using CF-Coater. As main factors for more effective MDRS of Diltiazem. HCl, ethylcellulose was used for the controlling drug release rate, and diethylphthalate was used for plasticizer, respectively. In vitro evaluation study was performed by comparative dissolution test between our test MDRS and reference Diltiazem. HCl preparation. The physical tests were performed using FT-IR and SEM. In vivo evaluation was also performed by observing the behavior of a plasma drug concentration after oral administration. The bioavailability was determined by analyzing the blood sample after oral administration to healthy, male volunteers once a day. As a result, there were no significant differences in bioequivalence parameters $(AUC_{\infty},\;C_{max},\;t_{1/2})$ between two systems. It might be concluded that our MDRS of Diltiazem. HCl could be an alternative delivery system to reference drug preparation.

• Journal of Pharmaceutical Investigation
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• v.38 no.6
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• pp.387-392
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• 2008

Alfuzosin, an Alphal-adrenoceptor antagonist is used for the treatment of patients with voiding and in a lesser extent storage lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH). The objective of this study was to formulate sustained release alfuzosin HCl granules and assess their formulation variables. The $Eudragit^{(R)}$ as a polymer, sustained release membrane, and dibutyl sebacate (DBS) as a plasticizer were used. Multi-coated alfuzosin HCl delivery systems composed of sugar sphere, various excipients, $Eudragit^{(R)}$ and HPMC (hydroxy propyl methyl cellulose), Cellulose Acetate were prepared by fluid-bed coater. Membrane layer were used $Eudragit^{(R)}$ RS PO and NE 30D. And the alfuzosin HCl coated beads were coated immediate release drug layer for initial burst. Its dissolution test was carried out compared to conventional products ($XATRAL^{(R)}$ XL). The release rate of drug from coated beads was higher than that from $XATRAL^{(R)}$ XL in pH 6.8.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.32 no.1
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• pp.10-16
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• 2021

Objectives: The aim of this study was to compare the compliance, efficacy, and satisfaction associated with methylphenidate and atomoxetine for treating attention-deficit/hyperactivity disorder (ADHD). Methods: The subjects were 44 patients who met the Diagnostic and Statistical Manual of Mental Disorder-5 diagnostic criteria for ADHD and were treated with methylphenidate or atomoxetine. The methylphenidate formulations included immediate release (IR), extended release (ER), and osmotic-controlled release oral delivery system (OROS). Patients and parents reported the average number of days per week the medication was taken. Efficacy was assessed using the ADHD Rating Scale. Satisfaction with medication scale (SAMS)-parent report form and SAMS-self-report form were used to evaluate parents' and patients' satisfaction, respectively. Results: Patients and parents were more satisfied with methylphenidate than with atomoxetine. There were no significant differences in the compliance with and efficacy of methylphenidate and atomoxetine. Compliance with methylphenidate IR and ER was markedly lower than that with OROS methylphenidate or atomoxetine. Conclusion: Methylphenidate OROS formulation can be considered a suitable option given its high rates of compliance, satisfaction, and efficacy.