• Journal of Pharmaceutical Investigation
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• v.40 no.5
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• pp.313-319
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• 2010

The objectives of this study were to evaluate the effect of formulation ingredients on the drug release and to optimize the novel sustained release matrix tablet formulations of bupropion hydrochloride. A three factor, three-level Box-Behnken design was used for the optimization procedure, with the amounts of PEO ($X_1$), citric acid ($X_2$) and Compritol 888 ATO ($X_3$) as the independent variables. The selected dependent variables were the cumulative percentage values of bupropion hydrochloride that had dissolved after 1, 4 and 8 hr. Various dissolution profiles of the drug from sustained release matrix tablets were obtained. Optimization was performed for $X_1$, $X_2$ and $X_3$ using the following target ranges; $30%{\leq}Y_1{\leq}45%$; $70{\leq}Y_2{\leq}85%$; $85%{\leq}Y_3{\leq}100%$. The optimized formulation for bupropion hydrochloride was achieved with 12.5% PEO ($X_1$), 2.5% citric acid ($X_2$) and 10% Compritol 888 ATO ($X_3$). The sustained release matrix tablets with the optimized formulation provided a release profile that was close to predicted values. In addition, the dissolution profiles of the sustained release matrix tablet with the optimized formulation were similar to those of the commercial product Wellbutrin$^{(R)}$ SR tablets ($f_2$=79.83).

• Journal of Pharmaceutical Investigation
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• v.41 no.1
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• pp.51-57
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• 2011

The objective of this study was to enhance the utilitization of Ibuprofen (IBU) by introducing the fast-disintegrating tablet (FDT) form. Presently, IBU is being widely used as a tablet or syrup form. But in contrast to these two formulations, IBU as FDT is not only convenient but also increases the control over the time release of the drug, noted by using Alginate beads. This study was carried out with Sodium Alginate and IBU at the ratios of 1:0, 1:0.5, 1:1, and 1:2 in order to produce a series of beads with different ratios. During the drying process of the beads, talc was added in beads to compare the effects with and without the talc. The final product was scanned with SEM imaging to determine the difference in the surface of the beads. The parameters assessed were the diameter, content assay, dissolution test and effectiveness of time-release. Direct compression method was used to prepare FDT containing IBU bead. The properties of FDT, such as hardness, disintegration time, were investigated. The dissolution profiles of FDT were tested using KP dissolution apparatus 1 (basket method). The results suggest addition of talc and drying the beads made the surface smooth and less vulnerable to clutter into chunks. The size of beads was less than 300 ${\mu}m$ which did not create a sandy feeling in the mouth. Thus, the beads formulation model made the sustained release of the drug possible, the hardness of FDT (1.25~1.50 $Kg/cm^2$) was acceptable and all the values of dissolving period were less than 30 seconds. The dissolution profile of FDT was same as that of IBU bead. The efficient dissolution profile and low price of IBU bead containing Sodium Alginate, the FDT formulation prepared from IBU bead can save the expenses and can improve the convenience of application of this drug.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.453-460
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• 2005

4-Aminopyridine (AP) is a potassium channel blocker used in the treatment of neurological disorders such as multiple sclerosis and Alzheimer disease. AP‘s window of therapeutic effect appears to correlate with its plasma halflife (3.5 hours). It demonstrates pH-dependent solubility because of a weakly basic drug. In addition, the resulting release from conventional matrix tablets decreases with increasing pH-milieu of the gastrointestinal tract. The aim of this study is to design sustained release matrix tablet containing AP, overcoming this problem. $Eudragit^{\circledR}$ L 100 (EuL) and sodium alginate were used in an effort to achieve pH independent drug release. The effect of sodium alginate and EuL on drug release from matrix tablet was investigated. The drug release behavior from the different tablets was analyzed by $t_{20%},\;t_{40%},\;t_{60%}$, The exponential diffusion coefficient n, kinetic constant K were calculated according to the Korsmeyer-Peppas equation. The drug release from matrix tablets prepared with sodium alginate was decreased with increasing the content of sodium alginate in pH 7.4 while there is no significant difference in pH 1.2. The exponent n values were determined to be approximately 0.5 and 0.8 respectively, in both pH 1.2 and 7.4. These values indicate diffusion-based anomalous mechanism and erosion-based anomalous mechanism, respectively. The drug release from sodium alginate matrix tablets prepared with solid dispersion of EuL containing drug showed a slow drug release in an acidic medium and a more fast drug release in phosphate medium, compared with sodium alginate matrix tablets prepared with physical mixture. These results may be attributed to the gel forming ability of sodium alginate and pH dependent solubility of EuL. Therefore, sustained-release AP matrix tablets using sodium alginate and EuL were successfully prepared.

• YAKHAK HOEJI
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• v.41 no.1
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• pp.48-59
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• 1997

Sustained release matrix tablets, pellets, and coated pellets for the delivery of sulindac were prepared using cellulose derivatives at various ratios, and evaluated for the dis solution pattern. The release of sulindac, from matrix tablets prepared with low viscosity HPMC was relatively fast, and especially the tablets made of Metolose SM released all of sulindac within 1 hr. The release of drug from tablets made of other HPMC derivatives were retarded in the order of the following: Pharmacoat 645>Pharmacoat 606>Pharrnacoat 606+HPC-L>HPC-L. The most sustained release pattern was observed with the preparation of high viscous polymer. Metolose 90 SH. While release of sulindac, from matrix type pellet containing 10mg/cap of Metolose 90 SH or 60 SH was completed within 1 hr, a prolonged release formulation (30% in 1 hr) was obtained by the inclusion of EC. Pellets coated with HPMC showed a fast release pattern (${\geq}$ 80% within 2 hrs), whereas pellets coated with HPMC and EC (molar ratio 1 : 1) showed a sustained release pattern (${\geq}$ 80% in 12 hrs), vath the release from EC pellets being the most sustained. Fast (naked) and slow release pellets coated with EC, Metolose 60SH 50cps and propylene glycol. and enteric pellets coated with HPMCP 55 and Myvacet$^{\circledR}$ were prepared, and combined at various ratios for the assessment of dissolution pattern. The result indicates the possibility that the development of 24 hr sustained release delivery systems containing sulindac for oral administration could be achieved by means of combining sustained and fast release pellets at a proper portion.

• Journal of Pharmaceutical Investigation
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• v.26 no.3
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• pp.187-192
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• 1996

The matrix tablet containing sodium alginate and $CaHPO_4$ can release drugs in a controlled fashion from hydrogel with gelling and swelling due to their interaction as water penetrates the matrices of the tablet. The purpose of this study was to evaluate release characteristics of the matrix tablet varying the amount of sodium alginate, $CaHPO_4$ and other excipients such as chitosan, hydroxypropyl methylcellulose (HPMC) and $Eudragit^{\circledR}$ RS100 in the simulated gastric and intestinal fluid. The practically soluble ibuprofen was used as a model drug. The release profiles of matrix tablet in the gastric fluid as a function of sodium alginate/$CaHPO_4$ ratio was not pronounced because of low solubility of drug and stability of alginate matrices. However, release rate of drug from the matrix tablet in the intestinal fluid was largely changed when sodium alginate/$CaHPO_4$ ratio was increased, suggesting that the ratio of sodium alginate/$CaHPO_4$ was an important factor to control the gelling and swelling of the matrix tablet. The incorporation of other excipients into the matrix tablet also influenced the release rate of drug. The chitosan and HPMC decreased the release rate of drug. No release of drug was occurred when $Eudragit^{\circledR}$ RS100 was added into the tablet. The retarded release of matrix tablet when excipients were added resulted from the hindrance of swelling and gelling of the matrix tablet containing sodium alginate and $CaHPO_4$. The hardness and bulk density of the matrix tablet was not correlated with release rate of drug in the study. From these findings, the ratio of sodium alginate and $CaHPO_4$ in the matrix tablet in addition to incorporation of excipients could be very important to control the release rate of drug in dosage form design.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.269-273
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• 2009

The objective of this investigation was to develop a gastro-retentive(GR) dosage form of gabapentin and was to evaluate of its dissolution characteristics. GR tablet consists of expandable core tablet matrix and semi-permeable membrane coating. Poloxamer 407 and sodium bicarbonate were used to prepare the core matrix. Polyvinly acetate dispersion (Kollicoat $SR30D^{(R)}$) and polyvinyl alcohol-polyethylene glycol copolymer ((Kollicoat $IR^{(R)}$)) were employed to form the semi-permeable membrane. The GR tablets significantly expanded up to fivefold in simulated gastrointestinal fluids with no apparent damage of the coating membrane over 12 hours. Also, the swelling rate was controllable with the amount of sodium bicarbonate. The drug release was observed to be substantially sustained based on coating level. The release rate of gabapentin from the GR tablet was gradually slowed down as the coasting amount was increased. The gabapentin GR tablet with 8% coating level showed a pseudo-zero order release kinetics over 12 hours. These results suggest that this swellable GR tablet system having semi-permeable membrane coating can be applicable for hydrophilic drug substances like gabapentin.

• Journal of Pharmaceutical Investigation
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• v.15 no.1
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• pp.32-39
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• 1985

Bioavailability studies in guinea pigs and dissolution tests of sustained release capsules of ascorbic acid were investigated comparing with those of solution. The results were as follows; 1. In the dissolution test sustained release capsules released 90% of ascorbic acid after 12 hours, and ascorbic acid in the chewable tablet was dissolved. completely within 10 minutes. 2. In the determination of total ascorbic acid concentration in serum, the area under the curve between 0 and 24 hours $(AUC\;0{\sim}24h)$ ana the maximum serum concentration $(C_{max})$ did not show any significant difference between solution and sustained release capsule. The time to the maximum concentration $(C_{max})$ and the time over $50{\mu}g/ml$ concentration showed significant difference. 3. The time reached to maximum excretion rate $(T_{max})$ in sustained release capsule was longer than that of solution.

• YAKHAK HOEJI
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• v.39 no.2
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• pp.185-192
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• 1995

Flurbiprofen, one of potent nonsteroidal antiinflammatory drugs, has several systemic side effects due to dose dumping effect following oral administration of its conventional solid dosage forms. To reduce these side effects and to sustain therapeutic concentration of the drug, matrix tablets of flurbiprofen were prepared and evaluated for sustained release from the tablets. The matrix tablets of flurbiprofen were prepared with Eudragit, Pluronic, (anhydrous) lactose and colloidal silicon dioxide employing two different preparation methods, wet granulation and direct compression. The dissolution rates of the tablets were evaluated using KP 2 method. Formulation factors that affected dissolution rates of flurbiprofen were the type and content of Eudragit, the type and content of Pluronic, and the tablet preparation method. Several formulations of the matrix tablets showed dissolution patterns close to the simulated profile using pharmacokinetic parameters of flurbiprofen.

• Journal of Pharmaceutical Investigation
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• v.40 no.5
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• pp.285-289
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• 2010

Manufacturing a multi-layered tablet such as Xatral XL$^{(R)}$ is more complex and expensive than monolayered tablets, but mono-layered tablets may have less favorable release properties depending on the pharmacodynamics and pharmacokinetics of the active ingredient. We therefore sought to develop a monolayer tablet with a similar dissolution profile to the commercial alfuzosin sustained-release triple layered tablet (Xatral XL$^{(R)}$). We prepared four different mono-layered alfuzosin tablets with different concentrations of hydroxypropyl methycellulose and PVP K-90. Fomulation III with alfuzosion/mg-stearate/ HPMC/ PVP K-90 (10/5/110/95 mg/tab) has a similar dissolution rate to Xatral XL$^{(R)}$, with a similarity factor score of 81.4. However, the swelling and erosion rates of the two formulations were different, and NIR analysis showed differences in the mechanisms of drug release. Thus, although formulation III and Xatral XL$^{(R)}$ show similar dissolution rates, the mechanisms of drug release are different.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.11
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• pp.7838-7843
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• 2015

In this study, metformin hydrochloride for first choice of type 2 diabetes patient is administered relatively high dose, 1000 to 2000 mg orally once a day, and had very high water solubility, so it make difficult to swallow tablet to requires high amount of sustained release agent. To overcome these challenges, we used novel metformin salts had relatively low water solubility to minimize sustaining excipient for small size of dosage form. six novel metformin salts were synthesized by making metformin free form under reaction with NaOH and adding acid salts. we confirmed metformin stearate had the lowest water solubility and showed half drug release in dissolution study at 12hour. In conclusion, novel metformin salts had low water solubility can be used to reduce the size of sustained metformin tablet for improving patient compliance.