Design and in vitro evaluation of zidovudine oral controlled release tablets prepared using hydroxypropyl methylcellulose

Oral controlled release matrix tablets of zidovudine were prepared using different proportions and different viscosity grades of hydroxypropyl methylcellulose. The effect of various formulation factors like polymer proportion, polymer viscosity and compression force on the in vitro release of drug were studied. In vitro release studies were carried out using United States Pharmacopeia (USP) type 1 apparatus (basket method) in 900 ml of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using Zero-order model equation, Higuchi's square-root equation and Ritger-Peppas' empirical equation. Compatibility of drug with various formulations excipients used was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 10% hydroxypropyl methylcellulose (HPMC) 4000 cps were found to show a good initial drug release of 21% in the first hour and extended the release upto 16 h. Matrix tablets containing 20% HPMC 4000 cps and 10% HPMC 15000 cps showed a first hour release of 18% and extended the release upto 20 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of zidovudine, with good initial release (17-25% in first hour) and which extend the release upto 16-20 h, can overcome the disadvantages of conventional tablets of zidovudine.     

Immediate release tablets of telmisartan using superdisintegrant-formulation, evaluation and stability studies

Telmisartan (anti-hypertensive) is insoluble in water; hence the drug may be slowly or incompletely dissolved in the gastro intestinal tract. So the rate of dissolution and therefore its bioavailability is less (bioavailability 42%). In the present study an attempt has been made to prepare immediate release tablets of telmisartan by using Polyplasdone XL-10 (Crosspovidone) at intragranular, extragranular and partly intra and extragranular level of addition to increase the rate of drug release from dosage form to increase the dissolution rate and hence its bioavailability. The prepared granules and tablets were evaluated for their physiochemical properties and in-vitro dissolution study was conducted for the prepared tablets. It was concluded that the immediate release tablets with proper hardness, disintegration time and with increase rate of dissolution can be made using Polyplasdone XL-10. Formuation-10 (F10) was selected for stability study and the in-vitro dissolution study showed that was no difference in percent of drug released between initial and sixth month sample.     

Properties of gastroretentive sustained release tablets prepared by combination of melt/sublimation actions of L-menthol and penetration of molten polymers into tablets

A novel floating sustained release tablet having a cavity in the center was developed by utilizing the physicochemical properties of L-menthol and the penetration of molten hydrophobic polymer into tablets. A dry-coated tablet containing famotidine as a model drug in outer layer was prepared with a L-menthol core by direct compression. The tablet was placed in an oven at 80°C to remove the L-menthol core from tablet. The resulting tablet was then immersed in the molten hydrophobic polymers at 90°C. The buoyancy and drug release properties of tablets were investigated using United States Pharmacopeia (USP) 32 Apparatus 2 (paddle 100 rpm) and 900 ml of 0.01 N HCl. The L-menthol core in tablets disappeared completely through pathways in the outer layer with no drug outflows when placed in an oven for 90 min, resulting in a formation of a hollow tablet. The hollow tablets floated on the dissolution media for a short time and the drug release was rapid due to the disintegration of tablet. When the hollow tablets were immersed in molten hydrophobic polymers for 1 min, the rapid drug release was drastically retarded due to a formation of wax matrices within the shell of tablets and the tablets floated on the media for at least 6 h. When Lubri wax? was used as a polymer, the tablets showed the slowest sustained release. On the other hand, faster sustained release properties were obtained by using glyceryl monostearate (GMS) due to its low hydrophobic nature. The results obtained in this study suggested that the drug release rate from floating tablets could be controlled by both the choice of hydrophobic polymer and the combined use of hydrophobic polymers.     

Floating and sustained-release characteristics of effervescent tablets prepared with a mixed matrix of Eudragit L-100-55 and Eudragit E PO

The aim of this study was to evaluate the influence of Na-bicarbonate as an effervescent agent on the floating and sustained-release characteristics in 0.1 M HCl of tablets made of Eudragit E PO (EE) and/or Eudragit L-100-55 (EL) as matrix formers at different EE:EL weight ratios: 0:100, 25:75, 50:50, 75:25, and 100:0. The tablets were made by direct compression utilizing metronidazole as a model drug. Effervescent tablets with 50EE/50EL (w/w) showed the best floating and sustained drug release properties in the dissolution medium. The corresponding noneffervescent tablets were nonfloating and showed significantly faster drug release. Effervescent tablets with single polymers showed an immediate drug release pattern. These results were explained by Fourier-transform infrared spectroscopy and elemental analysis, which showed strong evidence of interpolyelectrolyte complexation between EE and EL when they were exposed to 0.1 M HCl as an effervescent hybrid matrix, but not as a noneffervescent hybrid matrix. The role of Na-bicarbonate in allowing EE-EL complexation during dissolution was explained as due to raising the pH around EL particles for sufficient polymer ionization and ionic-interaction with the ionized EE.     

Tailoring Atomoxetine Release Rate from DLP 3D-Printed Tablets Using Artificial Neural Networks: Influence of Tablet Thickness and Drug Loading

Various three-dimensional printing (3DP) technologies have been investigated so far in relation to their potential to produce customizable medicines and medical devices. The aim of this study was to examine the possibility of tailoring drug release rates from immediate to prolonged release by varying the tablet thickness and the drug loading, as well as to develop artificial neural network (ANN) predictive models for atomoxetine (ATH) release rate from DLP 3D-printed tablets. Photoreactive mixtures were comprised of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 in a constant ratio of 3:1, water, photoinitiator and ATH as a model drug whose content was varied from 5% to 20% (w/w). Designed 3D models of cylindrical shape tablets were of constant diameter, but different thickness. A series of tablets with doses ranging from 2.06 mg to 37.48 mg, exhibiting immediate- and modified-release profiles were successfully fabricated, confirming the potential of this technology in manufacturing dosage forms on demand, with the possibility to adjust the dose and release behavior by varying drug loading and dimensions of tablets. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and microscopic analysis showed that ATH remained in a crystalline form in tablets, while FTIR spectroscopy confirmed that no interactions occurred between ATH and polymers.     

Optimization of salting-out taste-masking system for micro-beads containing drugs with high solubility

The salting-out taste-masking system is a multiparticulate system consisting of a drug core, a salting-out layer containing salts and water-soluble polymers, and a water-penetration control layer containing water-insoluble materials. The system generates a long lag time (time when released drug is less than 1%) for numbness masking, and a subsequent immediate drug release for high bioavailability. Aiming to contain the system and drugs that cause numbness in oral disintegrating tablets, the system was optimized to reduce the particle size and contain drugs with high water solubility in this study. The amount of coating on the layers, the coating solvent, and the positioning of the components were also optimized. The findings in this study will lead to the provision of numbness-masked oral disintegrating tablets to patients.     

Eudragit NE30D based metformin/gliclazide extended release tablets: formulation,characterisation and in vitro release studies

Metformin/Gliclazide extended release tablets were formulated with Eudragit NE30D by wet granulation technique. Two batches were prepared in order to study influence of drug polymer ratio on the tablet formation and in vitro drug release. The formulated tablets were characterized by disintegration time, hardness, friability, thickness, weight variation, and in vitro drug release. The percentage of polymer, with respect to Metformin/Gliclazide, required to produce tablets with acceptable qualities was 9 to 13.45. The percentage of polymer below this range released the drug immediately and above this range produced granules not suitable for tablet formation. The quantity of Metformin/Gliclazide present in the tablets and the release medium were estimated by a validated HPLC method. The formulated tablets had acceptable physicochemical characters and released the drug over 6-8 h. The data obtained from in vitro release studies were fitted with various kinetic models and was found to follow Higuchi kinetics.     

Thermal characteristics of poly (DL-lactic acid) microspheres containing neurotensin analogue.

The thermal characteristics of poly (DL-lactic acid) (DL-PLA) microspheres containing a hexapeptide (NA: H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt) with neurotensin activity were investigated. PLA microspheres with a drug content of 1.5-11.0% were prepared by a novel o/w (oil-in-water) solvent evaporation method. Both DL-PLA and NA were amorphous in form, and an increase in heat capacity at glass transition temperature (Tg) of the polymer was observed in DL-PLA microspheres containing NA. The Tg of DL-PLA (PLA2000 bulk) was 307.8 K, while Tg of microspheres containing NA (content 6.0%) shifted to 321.2 K. The Tg of PLA2000 microspheres was found to increase with an increase in the content of NA, and its increasing tendency reached a plateau at an NA content of greater than 6%. The apparent activation energy of glass transition of PLA2000 bulk and the microspheres was calculated to be 86.3 and 99.3 kcal/mol, respectively. As a result of the release test after storage at 4 degrees C and 40 degrees C for 1 month, nearly the same release profiles of NA from PLA2000 microspheres were found. The release rate of NA after the initial release became slow after storage at 45 degrees C for 1 month. This may be attributed mainly to a decrease in surface area caused by the formation of agglomerates of PLA2000 microspheres under conditions near Tg.     

Hydroxypropyl methylcellulose based cephalexin extended release tablets: influence of tablet formulation,hardness and storage on in vitro release kinetics

The object of this study was to develop hydroxypropyl methylcellulose (HPMC) based cephalexin extended release tablet, which can release the drug for six hours in predetermined rate. Twenty-one batches of cephalexin tablets were prepared by changing various physical and chemical parameters, in order to get required theoretical release profile. The influences of HPMC, microcrystalline cellulose powder (MCCP), granulation technique, wetting agent and tablet hardness on cephalexin release from HPMC based extended release tablets were studied. The formulated tablets were also characterized by physical and chemical parameters. The dissolution results showed that a higher amount of HPMC in tablet composition resulted in reduced drug release. Addition of MCCP resulted in faster drug release. Tablets prepared by dry granulation was released the drug slowly than the same prepared with a wet granulation technique. Addition of wetting agent in the tablets prepared with dry granulation technique showed slower release. An increase in tablet hardness resulted in faster drug release. Tablets prepared with a wet granulation technique and having a composition of 9.3% w/w HPMC with a hardness of 10-12 kg/cm(2) gave predicted release for 6 h. The in vitro release data was well fit in to Higuchi and Korsmeyer-Peppas model. Physical and chemical parameters of all formulated tablets were within acceptable limits. One batch among formulated twenty-one batches was successful and showed required theoretical release. The effect of storage on in vitro release and physicochemical parameters of successful batch was studied and was found to be in acceptable limits.     

Formulation and optimization of orally disintegrating tablets of sumatriptan succinate

The aims of the present research were to mask the intensely bitter taste of sumatriptan succinate and to formulate orally disintegrating tablets (ODTs) of the taste masked drug. Taste masking was performed by coating sumatriptan succinate with Eudragit EPO using spray drying technique. The resultant microspheres were evaluated for thermal analysis, yield, particle size, entrapment efficiency and in vitro taste masking. The tablets were formulated by mixing the taste masked microspheres with different types and concentrations of superdisintegrants and compressed using direct compression method followed by sublimation technique. The prepared tablets were evaluated for weight variation, thickness, hardness, friability, drug content, water content, in vitro disintegration time and in vitro drug release. All the tablet formulations disintegrated in vitro within 37-410 s. The optimized formulation containing 5% Kollidon CL-SF released more than 90% of the drug within 15 min and the release was comparable to that of commercial product (Suminat?). In human volunteers, the optimized formulation was found to have a pleasant taste and mouth feel and disintegrated in the oral cavity within 41 s. The optimized formulation was found to be stable and bioequivalent with Suminat?.     

The role of polymer/drug interactions on the sustained release from poly(dl-lactic acid) tablets

The release profiles of model drugs (propranolol HCl, diclofenac sodium, salicylic acid and sulfasalazine) from low molecular weight poly(d,l-lactic acid) [d,l-PLA] tablets immersed in buffer solutions were investigated in an attempt to explore the mechanism of the related phenomena. It was confirmed that drug release is controlled by diffusion through the polymer matrix and by the erosion of the polymer. The pH of the surrounding medium influences the drug solubility as well as swelling and degradation rate of the polymer and therefore the overall drug release process. Physicochemical interaction between d,l-PLA and drug is an additional factor which influences the degree of matrix swelling and therefore its porosity and diffusion release process. Propranolol HCl shows extended delivery time at both examined pH values (5.4 and 7.4) and especially at pH 7.4 where release was accomplished in 190 days, most probably due to its decreased solubility at higher pH values. The acidic drugs gave shorter delivery times especially at pH 7.4. A slower drug release rate and more extended delivery time at pH 7.4 in comparison with that at pH 5.4 was recorded for tablets loaded with diclofenac sodium and salicylic acid. The opposite effect was observed with samples loaded with propranolol HCl.     

Thermal characterization and compatibility studies of norfloxacin for development of extended release tablets

Norfloxacin (NFX) is a synthetic antibacterial drug. The development of extended release tablets improves the patients’ comfort and compliance, resulting in lower discontinuation of the therapy; with consequently decrease in bacterial resistance. In the present work, the thermal behavior of NFX was investigated using TG and DSC techniques. Isothermal and non-isothermal methods were employed to determine kinetic data of decomposition process. Compatibility studies between NFX and pharmaceutical excipients, including three hydrophilic polymers were carried out in order to develop a new formulation of NFX to obtain extended release tablets with an approved quality.     

Effect of decrease in both postprandial blood glucose (PBG) and fasting blood glucose (FBG) levels in normal beagle dogs with nateglinide enteric coated granules and immediate release tablets

Nateglinide is a new quick action/short duration (QRSD) type of oral blood glucose regulator, and nateglinide immediate release tablets are used for patients with mild diabetes under the trade name of Fastic((R)) tablets. In this study, we attempted to determine if it was possible to control both post-prandial blood glucose level (PBG) and fasting blood glucose level (FBG) for moderate or severe diabetes through controlled release of nateglinide. Enteric coated granules were selected for the administration form for controlled release of nateglinide, and three types of enteric coated granules were prepared having dissolution pH values of 5.5, 6.5 and 7.2. The three types of enteric coated granules were each administered separately or the enteric coated granules having an dissolution pH of 6.5 were administered simultaneous to administration of nateglinide immediate release tablets to normal beagle dogs just before feeding followed by measurement of plasma nateglinide concentration, plasma insulin concentration and blood glucose level. In the case of administering enteric coated granules alone (nateglinide: 9 mg/kg), the absorption of nateglinide was confirmed to tend to be delayed as the dissolution pH increased. In the case of an dissolution pH of 5.5, decreases in both PBG and FBG were observed. In the case of dissolution pH values of 6.5 and 7.2, only decrease in FBG was observed. In case of nateglinide immediate release tablets (nateglinide: 9 mg/kg), only decrease in PBG was observed. Decreases in both PBG and FBG were observed in the case of simultaneous administration of dissolution pH 6.5 enteric coated granules and nateglinide immediate release tablets just before feeding (nateglinide: 90 mg/head+60 mg/head). A correlation was observed between plasma nateglinide concentrations and blood glucose levels. On the other hand, there were no correlations observed between changes in plasma insulin concentrations and blood glucose levels. In case of nateglinide immediate release tablets (nateglinide: 150 mg/head), Decreases in both PBG and FBG were observed. However, the nateglinide controlled release formulation is more useful than the nateglinide immediate release tablets from the view point of avoidance of side effect, or of easy control of both PBG and FBG. On the basis of these results, the design of a controlled release formulation that contains nateglinide was suggested to enable control of both PBG and FBG for moderate and severe diabetes patients.     

Preparation of Losartan Potassium Controlled Release Matrices and In-Vitro Investigation Using Rate Controlling Agents

Controlled release matrices have predictable drug release kinetics, provide drugs for an extended period of time, and reduce dosing frequency with improved patient compliance as compared with conventional tablet dosage forms. In the current research work, losartan potassium controlled release matrix tablets were fabricated and prepared with rate altering agents; that is, Ethocel grade 100 combined with Carbopol 934PNF. Various drug to polymer ratios were used. HPMC, CMC, and starch were incorporated in some of the matrices by replacing some amount of filler (5%). The direct compression method was adopted for the preparation of matrices. In phosphate buffer (pH 6.8), the dissolution study was conducted by adopting the USP method-I as the specified method. Drug release kinetics was determined and dissolution profiles were also compared with the reference standard. Prolonged release was observed for all matrices, but those with Ethocel 100FP Premium showed more extended release. The co-excipient (HPMC, CMC, and starch) exhibited enhancement in the drug release rates, while all controlled release matrices released the drug by anamolous non-Fickian diffusion mechanism. This combination of polymers (Ethocel grade 100 with Carbopol 934PNF) efficiently extended the drug release rates up to 24 h. It is suggested that these matrix tablets can be given in once a day dosage, which might improve patient compliance, and the polymeric blend of Ethocel grade 100 with Carbopol 934PNF might be used in the development of prolonged release matrices of other water-soluble drugs.     

Simultaneous determination of atorvastatin and niacin in human plasma by LC-MS/MS and its application to a human pharmacokinetic study

A rapid, simple, sensitive and selective LC‐MS/MS method has been developed and validated for quantification of the atorvastatin (AT) and niacin (NA) in 250 μL human plasma. The analytical procedure involves a liquid–liquid extraction method using nevirapine as an internal standard (IS). The chromatographic separation was achieved on a Hypurity Advance (4.6 × 50 mm, 5 µm) column using a mobile phase consisting of 0.1% formic acid buffer–acetonitrile (20:80, v/v) at flow rate of 0.8 mL/min. The API‐4000 LC‐MS/MS was operated in the multiple‐reaction monitoring mode using electrospray ionization. The total run time of analysis was 3 min and elution of AT, NA and IS occurred at 1.06, 1.84 and 0.92 min, respectively. A detailed validation of the method was performed as per the US Food and Drug Administration guidelines and the standard curves found to be linear in the range of 0.10–30.0 ng/mL for AT and 20.2–6026 ng/mL for NA, with a coefficient of correlation of ≥0.99 for both the compounds. AT and NA were found to be stable in a battery of stability studies, viz. bench‐top, autosampler, re‐injection, wet‐extract and repeated freeze–thaw cycles. The developed assay method was successfully applied to a pharmacokinetic study in humans. Copyright © 2012 John Wiley & Sons, Ltd.     

Development of extended release coevaporates and coprecipitates of promethazine HCl with acrylic polymers: formulation considerations

The present investigation studied a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RLPO and Eudragit RS100 in different weight ratios (1 : 1 and 1 : 5) using coevaporation and coprecipitation techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM) as well as solubility and in vitro dissolution studies in 0.1 n HCl (pH 1.2), double distilled water and phosphate buffer (pH 7.4). Adsorption test from drug solution to solid polymers were also performed. Selected solid dispersion system was subjected to direct compression and compressed tablets were evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of coevaporates were related to increasing amount of polymers while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RLPO had a greater adsorptive capacity than Eudragit RS100 and thus its coevaporates in 1 : 5 ratio exhibited higher dissolution rate with 91.90% drug release for 12 h. Among different formulations, tablets prepared by Eudragit RLPO coevaporates (1 : 5) displayed extended release of drug for 12 h with 90.87% release followed by zero order kinetics (r(2)=0.9808).     

Modulation of Tenoxicam release from hydrophilic matrix: modulator membrane versus rate-controlling membrane

This paper describes the preparation of two layered device comprising of tenoxicam containing layer and a drug free membrane layer based on Geomatrix Technology. Our device based on bilaminated films which produced by a casting/solvent evaporation technique. The drug-hydroxypropyl methylcellulose (HPMC) layer was covered by drug free membrane layer composed of a mixture of different ratios of HPMC and ethyl cellulose (EC). The prepared devices were evaluated for thickness, weight, drug content uniformity, water absorption capacity and in-vitro drug release. The films were also evaluated for appearance, smoothness and transparency. The influence of drug free membrane layer composition and thickness on the drug release pattern was studied on 12 devices (D1 to D12). The results indicate that, the release of drug from HPMC matrixes without the drug free membrane layer was fast and follows diffusion controlled mechanism. The release of drug from the devices D1, D4, D9 and D12 follow the same mechanism, while the release of drug from other devices become linear with time (zero order) and extended for long time especially when thickness and the ratio of EC was increased in the drug free membrane layer. From this study it is concluded that, changing the geometry of drug layer by addition of drug free membrane layer and changing its composition and thickness plays an important role in determining whether the drug free membrane layer is rate-controlling or modulator membrane. Hence it can facilitate the development of different pharmaceutical products with different release pattern.     

Development and in vitro evaluation of ketoprofen extended release pellets using powder layering technique in a rotary centrifugal granulator

Powder layering technique was evaluated using laboratory scale centrifugal granulator instrument to prepare extended release pellet dosage form of ketoprofen. Ethyl cellulose and shellac polymers were used for drug layering and extended release coating in the same apparatus. Inert sugar spheres were intermittently treated with drug powder and binding solution. Combination of ethyl cellulose (45cps) and shellac was evaluated as binders at different levels (1:3 ratio, at 6%, 12%, 16% and 21%w/w polymer) for drug loading and for extended release coating (1:3 ratio at 2%, 4% and 7% w/w polymer). Pellets were evaluated for drug release study using paddle apparatus in pH 6.8 Phosphate buffer, 900ml at 100 rpm. Ethyl cellulose and shellac when used as binder during drug layering did not extend the ketoprofen release beyond 4h. However, coating of drug loaded pellets using ethyl cellulose and shellac resulted in extended release profile of ketoprofen for about 10h. Ethyl cellulose coating alone at a level of 3% w/w resulted in extended release profile. Coated pellets were evaluated for sphericity, Hardness-Friability Index and scanning electron microscopy. Scanning electron micrographs of the pellets showed a uniform coating of polymer on the core pellets substantiating the use of centrifugal granulator for extended release coating. Release pattern from the optimized batch was best explained by Higuchi's model. The drug release pattern from the pellets was found to be Non-Fickian anomalous type, involving both diffusion and erosion mechanism. Accelerated stability study of the coated pellets filled in hard gelatin capsule was conducted for 3-month period and observed for the effect on drug release profile.     

Development and evaluation of a monolithic floating drug delivery system for acyclovir

Acyclovir (ACV), a model drug for this study, is one of the most effective drugs against viruses of the herpes group. Absorption of orally administered ACV is variable and incomplete, with a bioavailability of ca. 15-30%. The drug is absorbed in the duodenum after oral administration and hence, preparation of a floating drug delivery system (FDDS) for ACV may increase oral absorption of the drug. ACV matrix tablets (200?mg) containing an effervescent base (sodium bicarbonate and citric acid) and a binary combination of hydroxypropyl methylcellulose (HPMC) K4M with carbopol or sodium carboxymethyl cellulose (Na CMC) or polyvinylpyrrolidone (PVP) and/or sodium alginate were prepared by the direct compression method. The tablets were evaluated for physicochemical properties and in vitro floating ability (floating lag-time and duration), bioadhesiveness and drug release. The drug release studies were carried out in 0.1?N HCl (pH 1.2) at 37±0.5°C. At appropriate time intervals, samples were withdrawn and assayed spectrophotometrically at λ(max)=259?nm. The floating test showed tablets containing 15% effervescent base had a floating lag time of 10-30?s and a duration of floating time of 24?h. The formulations containing HPMC-PVP, HPMC-Na CMC, HPMC-carbopol, and HPMC-sodium alginate released about 60-90% of their drug content during a 12-h period. Increasing carbopol caused slower drug release. We concluded that the proposed tablets with 15% effervescent base, 20-30% HPMC, 30% Na CMC (and/or 20% PVP or 20% sodium alginate) showed good floating and drug release properties in vitro, and should be considered as FDDS for ACV.     

Formulation approach for nicorandil pulsatile release tablet

The purpose of this study was to obtain a nicorandil pulsatile release tablet that has a well-regulated release lag time. When nicorandil is used as an antiangina drug, administration time control is important. A pulsatile release tablet is one of the effective approaches to modified release to reduce daily administration frequency. In this study, a pulsatile release tablet of nicorandil was formulated by fumaric acid dry coating around the core tablet including nicorandil. The model tablets, which had different content ratios of excipients in the dry-coating layer, were characterized by a dissolution test. The results showed that the release lag time was generated with fast release profiles. Various lag time controls of tablets were achieved, from 60 to 310 min on average, by variation of outer layer composition. From an analysis of the relation between lag times and outer layer composition, the key ingredient for prolongation of lag time was found to be fumaric acid. To analyze the lag time generation mechanism, water penetration for tablet was measured. The results indicated that the penetration depth was proportionate to the square root of time and the lag time formation mechanism was simple water penetration through the matrix of fumaric acid to the tablet core. The results also showed that the Washburn equation could be used to design the lag time of the pulsatile release tablet in this study. In conclusion, novel release control technology using fumaric acid was appropriate to obtain a nicorandil pulsatile release tablet that has well regulated lag time.