Development of Sustained-Release Tablets Containing Sodium Valproate: In Vitro and In Vivo Correlation

ABSTRACT

We have developed a 200 mg and 400 mg sustained-release sodium valproate tablet that allows effective blood concentration of the active drug with once-a-day dosing. The controlled dissolution or sustained release of the drug was attained by a membrane-controlled system. A single-coating system did not adequately control the dissolution rate, and therefore double-coated tablets were prepared and a human pharmacokinetic study was conducted. With the 200 mg VPA-Na tablets, the nonfasting C_max was only 20% higher than the fasting C_max. An in vitro dissolution test was conducted to predict the effects of food on drug dissolution after administration of this tablet. A relatively good correlation was observed between the absorption profiles and the dissolution profiles of the drug.     

A new in vitro/in vivo kinetic correlation method for nitrofurantoin matrix tablet formulations

The kinetic distributions of in vitro percentage release and in vivo percentage urinary excretion rates of nitrofurantoin from matrix tablets were plotted using a kinetic program. In vitro release rates were determined using the USP paddle and half-change methods. Urinary excretion curves of the drug were characterized by means of the statistical moments. The individual linear correlations between each in vitro and in vivo kinetic distribution were established, and regression equations were calculated. The application results of the best correlations obtained were evaluated according to in vivo results. A reversed kinetic procedure was applied for transformation of the correlated kinetic values to the drug percentage release rates. The modified Langenbucher kinetic showed excellent linear correlation (r = .9985). The method that is proposed in this study, the kinetic correlation program, is simple, independent of time, and suggests that it is possible to use kinetic distributions in the in vitro/in vivo correlation. This study also suggests using kinetic correlation to investigate the suitability of the in vitro dissolution methods with the in vivo drug dissolution.     

Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms

Objective: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied.

Materials and methods: Three modified-release formulations of aminophylline consisted of Carbopol® 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350?mg tablets, Srbolek, Serbia (R-I) and Phyllocontin^® 350, tablets Purdue Frederic, Canada (R-II).

Results: Calculated release rate constants and the ?2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher T_max, was found in the rabbits, dosed with F-II (12.00?h), F-III (10.50?h), and R-II (15.00?h) formulation. The highest C_max (9.22?mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58?mg/L) and R-II (4.18?mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L).

Discussion and conclusion: The results demonstrated a good correlation of Level A (r² = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.     

In vitro and in vivo investigation of taste-masking effectiveness of Eudragit E PO as drug particle coating agent in orally disintegrating tablets

Abstract

Context: Considering that bitter taste of drugs incorporated in orally disintegrating tablets (ODTs) can be the main reason for avoiding drug therapy, it is of the utmost importance to achieve successful taste-masking. The evaluation of taste-masking effectiveness is still a major challenge.

Objective: The objective of this study was to mask bitter taste of the selected model drugs by drug particle coating with Eudragit^® E PO, as well as to evaluate taste-masking effectiveness of prepared ODTs using compendial dissolution testing, dissolution in the small-volume shake-flask assembly and trained human taste panel.

Materials and methods: Model drugs were coated in fluidized bed. Disintequik? ODT was used as a novel co-processed excipient for ODT preparation. Selected formulations were investigated in vitro and in vivo using techniques for taste-masking assessment.

Results and discussion: Significantly slower drug dissolution was observed from tablets with coated drug particles during the first 3?min of investigation. Results of in vivo taste-masking assessment demonstrated significant improvement in drug bitterness suppression in formulations with coated drug. Strong correlation between the results of drug dissolution in the small-volume shake-flask assembly and in vivo evaluation data was established (R?≥?0.970).

Conclusion: Drug particle coating with Eudragit^® E PO can be a suitable approach for bitter taste-masking. Strong correlation between in vivo and in vitro results implicate that small-volume dissolution method may be used as surrogate for human panel taste-masking assessment, in the case of physical taste-masking approach application.     

Evaluation of monolithic osmotic tablet system for nifedipine delivery in vitro and in vivo

The aim of this study was to evaluate the monolithic osmotic tablet system (MOTS) containing a solid dispersion with the practically water-insoluble drug nifedipine in vitro and in vivo. In the drug release study in vitro, the release profiles of this system had almost zero-order kinetics. The influences of tablet formulation variables, sizes of the delivery orifice, membrane variables, and values of pH in the dissolution medium on nifedipine release from MOTS have been investigated. The results provided evidence that the tablet core played an important role in MOTS. While orifice sizes and membrane variables affected the nifedipine release rate, MOTS was independent of the dissolution medium. The appropriate orifice size was found to be in the range of 0.5-1.0 mm. The coating membrane incorporating hydrophilic polyethylene glycol (PEG) formed a porous structure. The human pharmacokinetics and relative bioavailability of MOTS containing nifedipine were compared with a commercial Adalat® osmotic tablet system containing an equivalent dose of nifedipine following an oral single dose of 30 mg given to each of 11 healthy volunteers in an open, randomized crossover study in vivo. The relative bioavailability for MOTS was 112%. There was no statistically significant difference in the pharmacokinetic parameters between two dosage forms. It is concluded that the monolithic osmotic tablet controlled release system is feasible for a long-acting preparation as a once-daily treatment.     

In vitro-in vivo correlation and comparative bioavailablity of vincamine in prolonged-release preparations

Developing an in vitro dissolution test that gives good correlation with in vivo data for a particular drug product is an important objective. Available dissolution data of vincamine prolonged-release preparations show different in vitro release behavior at different pH using the conventional dissolution techniques. This does not allow development of an in vitro-in vivo correlation (IVIVC). In the present work, the flow-through cell (FTC) dissolution system (USP apparatus 4) was utilized to compare the release rate of three marketed prolonged-release oral formulations of vincamine; namely, a brand innovator formulation used as the reference and two formulations from different manufacturers as test products. Both the open and closed systems of FTC were used at variable pH. A comparative bioavailability study was then conducted in 16 healthy volunteers for a test versus the reference product by administering a single dose of 60 mg in a crossover design. Vincamine plasma concentrations were analyzed by a sensitive high-performance liquid chromatography (HPLC) method. This was followed by assessment of IVIVC according to level A as specified by USP 23; the absorbed fraction of vincamine was determined using the Wagner-Nelson method. The results indicated that the pH of the medium affects the release rate pronouncedly. The relative bioavailability based on C_max and AUC_0-12 were found to be 83.15% and 84.15%, respectively. Good correlation was obtained between fraction absorbed in vivo and fraction dissolved in vitro by applying the open system of the FTC. This technique gave the most favorable results with regard to the percentage vincamine released and the IVIVC     

Studies on bi-layer osmotic pump tablets of water-insoluble allopurinol with large dose: in vitro and in vivo

Controlled release bi-layer osmotic pump tablets (BOPT) of water—insoluble allopurinol with large dose (150 mg/BOPT) were successfully prepared merely with sodium chloride as osmotic promoting agent and polyethylene oxide (PEO) as suspending agent. Formulations of the two kinds of agents were investigated in order to discuss their effects on the release behavior of BOPT, and then the optimal formulation was evaluated. The pharmacokinetics studies of allopurinol and its active metabolite oxypurinol in two-preparation and two-period crossover design relative to the equivalent dose of commercially common allopurinol tablets were evaluated in six Beagle dogs. And the pharmacokinetics results showed that allopurinol BOPT were able to provide a slow release of allopurinol, and oxypurinol were bioequivalent between allopurinol BOPT and common allopurinol tablets. A good in vitro-in vivo correlation of allopurinol was also proved. In conclusion, water-insoluble drugs with large dose can be designed to BOPT for efficacy and safety use.     

In vitro dissolution method fitted to in vivo absorption profile of rivaroxaban immediate-release tablets applying in silico data

Objective: This study aimed to develop and validate an in vitro dissolution method based on in silico–in vivo data to determine whether an in vitro–in vivo relationship could be established for rivaroxaban in immediate-release tablets.

Significance: Oral drugs with high permeability but poorly soluble in aqueous media, such as the anticoagulant rivaroxaban, have a major potential to reach a high level of in vitro–in vivo relationship. Currently, there is no study on scientific literature approaching the development of RIV dissolution profile based on its in vivo performance.

Methods and results: Drug plasma concentration values were modeled using computer simulation with adjustment of pharmacokinetic properties. Those values were converted into drug fractions absorbed by the Wagner–Nelson deconvolution approach. Gradual and continuous dissolution of RIV tablets was obtained with a 30?rpm basket on 50?mM sodium acetate +0.2% SDS, pH 6.5 medium. Dissolution was conducted for up to 180?min. The fraction absorbed was plotted against the drug fraction dissolved, and a linear point-to-point regression (R²?=?0.9961) obtained.

Conclusion: The in vitro dissolution method designed promoted a more convenient dissolution profile of RIV tablets, whereas it suggests a better relationship with in vivo performance.     

Celecoxib-cyclodextrin systems: characterization and evaluation of in vitro and in vivo advantage

Solid dispersions of Celecoxib were prepared with hydroxypropyl β cyclodextrin by various methods such as physical mixture, cogrinding, kneading, and coevaporation. The dispersions were characterized by differential scanning calorimetry (DSC), X-ray diffraction patterns, infrared spectroscopy, and nuclear magnetic resonance studies. The DSC thermograms of the dispersions indicated potential of heat-induced interaction between Celecoxib and cyclodextrin that could influence in vitro drug dissolution. The dispersions exhibited faster rates of dissolution compared to that of Celecoxib. The kneaded dispersion with the fastest in vitro dissolution rate when compressed into tablets showed a better release profile compared to the tablets of pure Celecoxib. In vivo studies revealed that the kneaded dispersion provided for quicker response and was more effective in inhibiting rat paw edema as compared to Celecoxib alone, thus confirming the advantage of improved pharmacological activity of Celecoxib when administered as a solid dispersion with cyclodextrin.     

In vitro and in vivo release of naltrexone from biodegradable depot systems

The aim of this study was to prepare poly(d, l-lactide) (PLA) microspheres containing naltrexone (NTX) by a solvent evaporation method, and to evaluate both in vitro and in vivo release characteristics and histopathological findings of tissue surrounding an implant formulation in rats.

This method enabled the preparation of microspheres of regular shape and relatively narrow particle size distribution. The in vitro release profiles of NTX from PLA microspheres showed the release of NTX did not follow zero-order kinetics. An initial burst release was observed, subsequently followed by a nearly constant rate of 0.4% per day after ten days. The cumulative amount of NTX released at the end of 60 days was 80%. Compressed microspheres showed near zero-order sustained release of NTX for 360 days. The plasma NTX levels in rats showed that for compressed microspheres NTX concentrations were constant and exceeded 2 ng/mL for 28 days. Throughout the 28 days of study, the implantations cause a minor inflammatory response, which can be regarded as a normal defence mechanism. The sustained release performance of NTX from the biodegradable depot systems may provide a reliable, convenient, and safe mechanism for the administration of NTX for the long-term treatment of opioid dependence.     

Considerations in the development of an in vitro dissolution condition for lacidipine tablets: in vivo pharmacokinetic evaluation

In this study, a new discriminative dissolution condition for lacidipine tablets was developed by the established in vitro–in vivo relationship. Series of dissolution media of phosphate buffer solution (PBS) covering the pH range of 1–7.2 and pH 6.8 PBS containing different concentrations of sodium dodecyl sulfate (SDS), were prepared and used to investigate the dissolution behavior of lacidipine tablets. There was an obvious difference in the dissolution profiles of the both brands in pH 6.8 PBS medium containing 0.1% SDS. The pharmacokinetic study of the two lacidipine tablets was carried out in the healthy beagle dogs at a single dose of 4?mg. Statistical comparison of the AUC_0–24, C_max, and T_max showed a significant difference in the two brand tablets, coinciding with the dissolution performance with pH 6.8 PBS containing 0.1% SDS. The superiority of the proposed system, pH 6.8 PBS containing 0.1% SDS, could serve as a dissolution medium for lacidipine tablets, and more important it could discriminate the in vivo pharmacokinetic behavior for different brands of products. In summary, in vivo pharmacokinetic evaluation is essential to develop an appropriate in vitro dissolution condition for oral solid dosage forms of poorly soluble drugs.     

Study on the release of fenofibrate nanosuspension in vitro and its correlation with in situ intestinal and in vivo absorption kinetics in rats

As an oral delivery carrier for poorly water soluble drugs, the nanosuspension was prepared by melt emulsification method combined with high-pressure homogenization. The objective of this study was to clarify the absorption mechanism in rats of fenofibrate nanosuspension using the model of in situ gut perfusion. The release rate of drug from nanosuspension was fast which about 70% of the drug would be released within 5 minutes. The absorption of fenofibrate nanosuspension in the gastrointestinal (GI) tract was studied by the in situ closed loop method in rats. It was found that the absorption process in intestine was first-process with passive diffusion mechanism, and the whole intestine was the major segment for the drug absorption. Additionally, GI absorption in situ studies indicated that the fenofibrate nanosuspension had great success in regard to enhancement of intestinal absorption compared to the fenofibrate suspension of coarse powder. The pharmacokinetic characteristics were studied in rats after oral administration of fenofibrate nanosuspension or suspension at the dosage of 27?mg/kg. The plasma concentration-time curve was fitted to the one-compartment model. The correlation between in vitro dissolution (P), in situ intestinal absorption (F) and in vivo absorption (Fa) in rats was investigated with the results as follows: Fa?=?6.2061P–456.38(r?=?0.9559), F?=?3.6911P–2.2169(r?=?0.970), F?=?0.5095P?+?44.189(r?=?0.9609). The highest level A could be obtained from the in vitro--in vivo correlation (IVIVC) between dissolution percentage and intestinal absorption of the fenofibrate nanosuspension in rats. Consequently, the in situ intestinal perfusion model could be used to predict the in vivo pharmacokinetic characteristics in rats.     

In vitro and in vivo evaluation of cubosomal in situ nasal gel containing resveratrol for brain targeting

The aim of this study was to enhance the delivery of resveratrol to the brain through the transnasal route by cubosomes. Cubosomes were prepared using glycerol monooleate and Lutrol F127 by probe sonication method. A 3² full factorial design was used for optimization of cubosomes and batch containing 4% w/v glycerol monooleate and 1.5% w/v of Lutrol F 127 was optimized. The selected cubosomal batch was cubical in shape, having mean particle size 161.5?±?0.12?nm. Entrapment efficiency was found to be 83.08% with zeta potential of –20.9?mV. In vitro release of cubosomal batch showed controlled release of drug profile (67%) up to 24?h. The optimized cubosomal dispersion was dispersed into gelling polymer (poloxamer 407) to form in situ gel for nasal use. The optimal cubosomal gel (containing 12% w/v poloxamer 407) had been subjected to ex-vivo permeation and in vivo biodistribution studies. It showed significantly higher transnasal permeation and better distribution to brain, when compared to the drug solution (i.n.) and drug solution (oral). Finally the cubosomal gel could be considered as a promising carrier for brain targeting of Resveratrol (Res) through transnasal route.     

Development of Monolithic Osmotic Pump Tablet System for Isosorbide-5-Mononitrate Delivery and Evaluation of it In Vitro and In Vivo

The objective of this study is to develop the monolithic osmotic pump tablet system (MOTS) containing isosorbide-5-mononitrate (5-ISMN), and to evaluate its in vitro and in vivo properties. The influences of tablet formulation variables, size and location of the delivery orifice, membrane variables, and pH value of the dissolution medium on 5-ISMN release from MOTS have been investigated. These results demonstrated that the tablet core played an important role in MOTS, and membrane variables could affect the 5-ISMN release rate. The optimal formulation of 5-ISMN MOTS was determined by uniform design. Furthermore, the dog pharmacokinetics and relative bioavailability of the test formulation (5-ISMN MOTS) have been compared with the reference formulation (Imdur^®: 60 mg/tablet, a sustained release, SR, tablet system) following an oral single dose of 60 mg given to each of six Beagle dogs. The mean drug fraction absorbed by the dog was calculated by the Wagner–Nelson technique. The results showed that drug concentration in plasma could be maintained more stable and longer after the administration of 5-ISMN MOTS compared with the matrix tablets of Imdur^®, and a level A “in vitro–in vivo correlation” was observed between the percentage released in vitro and percentage absorbed in vivo. It is concluded that 5-ISMN MOTS is more feasible for a long-acting preparation than 5-ISMN SR tablet system as once-a-day treatment, and it is very simple in preparation, and can release 5-ISMN at the rate of approximately zero order for the combination of hydroxypropylmethyl cellulose as retarder and NaCl as osmogent.     

Studies on the in vitro and in vivo degradation behavior of amino acid derivative-based organogels

The in vitro degradation behavior of organogel with different gelators based on amino acid was investigated in detail. Two methods were applied in this research: weighting method and high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) method, which was established for the first time. Their degradation behaviors in vivo were investigated by varying the kind and concentration of gelators via subcutaneous implantation. The results showed that the stronger the gelation ability or the higher the gelator concentration, the slower the degradation rate of organogel. Moreover, the organogel prepared by oils with longer alkyl length degraded slower than that of the shorter ones, which also decreased in thermal stability and mechanical strength. The investigation on degradation process showed that the degradation rate was mainly controlled by the collapse of network structure formed by gelators. In conclusion, organogel had a tunable degradation rate through altering the gelator type, oil type and the gelator concentration. It remains a promising candidate for subcutaneous in-situ implant as drug delivery vehicle.     

Gemifloxacin mesylate (GFM): dissolution test based on in vivo data

Gemifloxacin mesylate (GFM) is a synthetic, broad-spectrum, fluoroquinolone antibacterial agent. It is different from other class members because it achieves adequate plasma concentrations to inhibit both topoisomerase IV and gyrase. The aim of this study was to develop and validate a dissolution test for GFM in coated tablets, using a simulated absorption profile based on in vivo data obtained from the literature. The fraction and percentage of the dose absorbed were calculated using model-dependent Loo-Riegelman approach for two compartments. The best in vitro dissolution profile was obtained using 900?mL of pH 6.0 phosphate buffer as a dissolution medium at 37?°C?±?0.5?°C and paddles at 50?rpm. The in vitro dissolution samples were analyzed using a liquid chromatography method, and the validation was performed according to USP 34 (2011). The method showed specificity, precision, accuracy, robustness and linearity. Under these conditions, a level-A in vitro–in vivo correlation was suggested (r?=?0.9926). The prediction errors were calculated to determine the validity and accuracy of the suggested correlation. The dissolution test can be used to evaluate the dissolution profile of GFM-coated tablets and minimize the number of bioavailability studies as part of new formulation development.     

Effect of semicrystalline copolymers in solid dispersions of pioglitazone hydrochloride: in vitro-in vivo correlation

Objective: The study was aimed to improve the dissolution and bioavailability of developed stable amorphous solid dispersions (SDs) of pioglitazone hydrochloride (PGH), a poorly water-soluble drug.

Significance: Poor aqueous solubility of PGH was overcome by the design of SDs. Level A correlation demonstrated between in vitro release and bioavailability of PGH, suggest its biowaiver potential.

Methods: The effects of semicrystalline copolymers (poloxamer 407 and gelucire 50/13) and methods of preparations on dissolution behavior, in vivo performance, and stability of PGH SDs were investigated. All the SDs were characterized by FTIR, TGA, DSC, XRD, and SEM.

Results: FTIR and TGA showed the compatibility with the polymers. The significant change in melting pattern of the PGH observed in the DSC thermograms supported by XRD patterns & SEM indicated a change from a crystalline to an amorphous state. Gelucire 50/13 was observed to have greater ability to form SDs than poloxamer 407 in solvent evaporation method (SM). Prevention of recrystallization during storage suggested stability of the formulation. Gelucire 50/13 based SD, prepared by SM remarkably increased the dissolution within 15?min (87.27?±?2.25%) and was supported by dissolution parameters (Q₁₅, IDR, RDR, % DE, f₁, f₂). These SDs showed pH-dependent solubility. In vivo test showed significantly (p?<?.05) higher AUC_0–t and C_max, which were about 3.17 and 4.34 times that of the pure drug respectively.

Conclusion: Gelucire 50/13 was found to be a suitable carrier for SM for preparation of SDs of PGH as evident from increased dissolution and bioavailability.     

A New Rapidly Absorbed Paracetamol Tablet Containing Sodium Bicarbonate. II. Dissolution Studies and In Vitro/In Vivo Correlation

ABSTRACT

The objective of this study was to compare the in vitro dissolution profile of a new rapidly absorbed paracetamol tablet containing sodium bicarbonate (PS) with that of a conventional paracetamol tablet (P), and to relate these by deconvolution and mapping to in vivo release. The dissolution methods used include the standard procedure described in the USP monograph for paracetamol tablets, employing buffer at pH 5.8 or 0.05 M HCl at stirrer speeds between 10 and 50 rpm. The mapping process was developed and implemented in Microsoft Excel® worksheets that iteratively calculated the optimal values of scale and shape factors which linked in vivo time to in vitro time. The in vitro–in vivo correlation (IVIVC) was carried out simultaneously for both formulations to produce common mapping factors. The USP method, using buffer at pH 5.8, demonstrated no difference between the two products. However, using an acidic medium the rate of dissolution of P but not of PS decreased with decreasing stirrer speed. A significant correlation (r = 0.773; p<.00001) was established between in vivo release and in vitro dissolution using the profiles obtained with 0.05 M HCl and a stirrer speed of 30 rpm. The scale factor for optimal simultaneous IVIVC in the fasting state was 2.54 and the shape factor was 0.16; corresponding values for mapping in the fed state were 3.37 and 0.13 (implying a larger in vitro–in vivo time difference but reduced shape difference in the fed state). The current IVIVC explains, in part, the observed in vivo variability of the two products. The approach to mapping may also be extended to different batches of these products, to predict the impact of any changes of in vitro dissolution on in vivo release and plasma drug concentration–time profiles.     

Improved initial burst of estradiol organogel as long-term in situ drug delivery implant: formulation,in vitro and in vivo characterization

Objective: The present investigation was aimed at optimizing of estradiol (E2) loaded l-amino acid derivatives organogel formulations resulting in improved the high initial release problems and sustained release of E2.

Methods: The visco-elastic properties of blank organogels were measured by rheometer. The E2 organogel formulations were optimized using a central composite design. Also, the effect of gelator structure and composition of the gel formulations on release behavior (in vitro and in vivo) had been studied.

Results: The change of the gelator structure could affect significantly the stiffness of the implants. The release behavior of gel without N-Methyl-2-pyrrolidinone (NMP) was controlled by gel corrosion only. While the drug release of the gel with NMP was controlled by both corrosion and diffusion. The high initial release problems of the organogels were improved by optimizing the formulations. The system consisting by N-Lauroyl l-lysine methyl ester (LLM) derivative in the oil indicated the lowest initial drug release, showed a much lower blood drug level and maintained a steady state for nearly 1 month.

Conclusion: Organogels based on l-lysine methyl ester derivative were ideal carriers for long-term parenteral administration of E2.     

In vitro and in vivo evaluation of hydrophilic and hydrophobic polymers-based nicorandil-loaded peroral tablet compared with its once-daily commercial sustained-release tablet

Context: Hydrophilic and hydrophobic polymer-based nicorandil (10 mg)-loaded peroral tablets were prepared using the wet granulation technique. The influence of varying amounts of hydroxypropyl methylcellulose (HPMC) (30–50 mg), ethylcellulose (2–4 mg), microcrystalline cellulose (5–20 mg) and Aerosil^® (5–12 mg) in conjunction with the constant amounts (3 mg) of glidant and lubricant (magnesium stearate and talc) on the in vitro performances of the tablets (hardness, friability, weight variation, thickness uniformity, drug content, and drug release behavior) were investigated. Objective: The objectives of this study were (i) to select a nicorandil-loaded peroral tablet that matched the in vitro dissolution profile of once-daily commercial sustained-release tablet, and (ii) to compare the in vivo sustaining/controlling efficacy of the selected peroral tablet with that of its commercial counterparts. Results and Discussion: Because the nicorandil (10 mg)-loaded tablet prepared based on F-IX composition (50 mg HPMC, 4 mg ethylcellulose, 10 mg MCC and 3 mg glidant and lubricant) showed a release profile comparable to that of the Nikoran^® OD SR tablet release profile, the tablet with this composition was considered to be the optimized/selected formulation and, therefore, was subjected to stability study and in vivo study in rabbits. Despite of the higher C_max and AUC values obtained with the optimized tablet, there was no sign of difference between the optimized- and Nikoran^® OD SR- tablets following a single-dose crossover oral administration into rabbit. Conclusion: The optimized tablet could be used as an alternative to the commercial once-daily tablet.