Pulsatile Release Profile Research Articles

Development of 3D-Printed Two-Compartment Capsular Devices for Pulsatile Release of Peptide and Permeation Enhancer.

The oral absorption of a peptide is driven by a high local concentration of a permeation enhancer (PE) in the gastrointestinal tract. We hypothesized that a controlled release of both PE and peptide from a solid formulation, capable of maintaining an effective co-localized concentration of PE and peptide could enhance oral peptide absorption. In this study, we aimed to develop a 3D-printed two-compartment capsular device with controlled pulsatile release of peptide and sodium caprate (C10). 3D-printed two-compartment capsular device was fabricated using a fused deposition modeling method. This device was then filled with LY peptide and C10. The release profile was modulated by changing the thickness and polymer type of the capsular device. USP apparatus II dissolution test was used to evaluate the impacts of device thickness and polymer selection on release profile in vitro. An optimal device was then enteric coated with HPMCAS. A strong linear relationship between the thickness of capsular devices and the delay in the release onset time was observed. An increase in the device thickness or the use of PLA decreased the release rate. The capsular device with compartment 1, compartment 2 and fence thickness of 0.4; 0.95 and 0.5mm, respectively, and the use of PVA achieved desired pulsatile release profiles of both peptide and C10. Furthermore, enteric-coated capsular devices with HPMCAS had similar pulsatile release profiles compared to non-enteric coated devices. These findings suggest potential application of 3D-printing techniques in the formulation development for complex modified drug release products.

Corked Microcapsules Enabling Controlled Ultrasound-Mediated Protein Delivery.

While ultrasound represents a facile, portable, and noninvasive trigger for drug delivery vehicles, most reported ultrasound-triggered drug delivery vehicles predominately present "burst" release profiles that are hard to control after the initial activation stimulus. Herein, we report a submerged electrospraying technique to fabricate protein-loaded microcapsules in which silica "corks" are embedded within the microcapsule shell. Upon the application of an ultrasound trigger, the corks can be perturbed within the shell, allowing for the release of the protein payload through a phantom tissue mimic to a degree proportional to the number/time of pulses applied. Specifically, multiple ultrasound pulses were shown to enable a 15- to 23-fold increase in the rate of release of the model bovine serum albumin protein payload relative to no ultrasound being applied, with release returning to a lower level when the ultrasound stimulus was removed. Coupled with the low cytotoxicity of the vehicle components, the corked microcapsules show promise for expanding the potential to use ultrasound to facilitate both on-demand and pulsatile release profiles.

Colon Drug Delivery Systems Based on Swellable and Microbially Degradable High-Methoxyl Pectin: Coating Process and In Vitro Performance.

Oral colon delivery systems based on a dual targeting strategy, harnessing time- and microbiota-dependent release mechanisms, were designed in the form of a drug-containing core, a swellable/biodegradable polysaccharide inner layer and a gastroresistant outer film. High-methoxyl pectin was employed as the functional coating polymer and was applied by spray-coating or powder-layering. Stratification of pectin powder required the use of low-viscosity hydroxypropyl methylcellulose in water solution as the binder. These coatings exhibited rough surfaces and higher thicknesses than the spray-coated ones. Using a finer powder fraction improved the process outcome, coating quality and inherent barrier properties in aqueous fluids. Pulsatile release profiles and reproducible lag phases of the pursued duration were obtained from systems manufactured by both techniques. This performance was confirmed by double-coated systems, provided with a Kollicoat® MAE outer film that yielded resistance in the acidic stage of the test. Moreover, HM pectin-based coatings manufactured by powder-layering, tested in the presence of bacteria from a Crohn's disease patient, showed earlier release, supporting the role of microbial degradation as a triggering mechanism at the target site. The overall results highlighted viable coating options and in vitro release characteristics, sparking new interest in naturally occurring pectin as a coating agent for oral colon delivery.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer (TNBC), a highly aggressive disease with a poor prognosis. This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals, allowing for promising clinical outcomes with intensive treatment. However, the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance, limiting therapeutic efficacy and clinical benefit. Here, we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with time-programmed pulsatile release profiles. The implantable device can control the time between drug releases based on its internal microstructure design, which can be used to control dose density. The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar. Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo. Under the same dose density conditions, device-based chemotherapy shows a higher anti-cancer effect and less toxic response than intratumoral injection. We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose, number of releases, and treatment duration of the dose-dense AC (doxorubicin and cyclophosphamide) regimen preferred for TNBC treatment. Dose density modulation inhibits tumor growth, metastasis, and the expression of drug resistance-related proteins, including p-glycoprotein and breast cancer resistance protein. To the best of our knowledge, local dose-dense chemotherapy has not been reported, and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

Dual-Cross-Linked Magnetic Hydrogel with Programmed Release of Parathyroid Hormone Promotes Bone Healing.

Intermittent delivery of parathyroid hormone (PTH) could effectively promote bone regeneration, but the need for daily injection administration has limited its further clinical applications. Exposure to magnetic stimulation could regulate cell fate to promote osteogenesis. Herein, we developed a magnetized hydrogel with programmed PTH release and simultaneous magnetic actuation to promote osteogenic commitment. Ag dual-cross-linked hydrogel was formulated as GelMA-PVA (GP) biphasic reservoir with magnetic nanoparticles (GPM) and PTH (GPMP). Macroscopic and microscopic characterizations were performed to optimize the formulations. In vitro release assessment confirmed the programmable release of PTH with a pulsatile profile primed via magnetization in the first 4 days and a sustained release, controlled by an optimized GP matrix, for over a month. Stimulated by an alternating magnetic field, the hydrogels displayed a zigzag-shaped pulsatile release profile, and the cumulative release was enhanced by 8, 28, and 18% in In40, Ab40, and In20Ab20 (loading 40 μg PTH via incorporation, absorption, and their combination) formulations, respectively, compared with the same formulations without magnetic stimulation. An in vitro cytocompatibility test showed that all formulations were biocompatible and that PTH addition significantly promoted the proliferation of MC3T3-E1 pre-osteoblasts. In vivo studies presented enhanced new bone regeneration with significantly improved bone volume and bone mineral density in GPM and GPMP groups (increased by 120 and 251% compared with those of non-treated control), confirming their osteogenic effects and accelerated bone healing. This newly developed GPMP sample provides simultaneous osteogenesis effects via the programmed release of PTH and magnetically promoted bone regeneration and is promising in the facilitation of bone healing and treatment of various delayed/non-union conditions without the burden of daily injection.

In vitro and in vivo evaluation of a pH-, microbiota- and time-based oral delivery platform for colonic release

Several formulation strategies have been proposed for oral colon delivery, particularly for the therapy of inflammatory bowel disease (IBD). However, targeting the large intestine remains a challenging goal. The aim of this study was to develop and evaluate a novel type of drug delivery system, which is based on multiple drug release triggers for reliable performance. The system consists of: (i) a drug core, (ii) an inner swellable low-viscosity hydroxypropyl methylcellulose (HPMC) layer, and (iii) an outer film coating based on a Eudragit® S:high-methoxyl (HM) pectin (7:3 w/w) blend, optionally containing chitosan. Convex immediate release tablets (2 or 4 mm in diameter) containing paracetamol or 5-aminosalicylic acid (5-ASA) were coated in a fluid bed. The double-coated tablets exhibited pulsatile release profiles when changing the release medium from 0.1 N HCl to phosphate buffer pH 7.4. Also, drug release was faster in simulated colonic fluid (SCF) in the presence of fecal bacteria from IBD patients compared to control culture medium from tablets with outer Eudragit® S: HM pectin: chitosan coatings. The latter systems showed promising results in the control of the progression of colitis and alteration of the microbiota in a preliminary rat study.

Formulation and In Vitro Evaluation of Pellets Containing Sulfasalazine and Caffeine to Verify Ileo-Colonic Drug Delivery.

The ColoPulse coating is a pH-dependent coating that can be used to target drug release to the ileo-colonic region. ColoPulse coated tablets and capsules have demonstrated their targeting capabilities in vivo in more than 100 volunteers and patients. However, so far the ColoPulse coating has not been used for multi-particulate pellet formulations. The sulfasalazine–caffeine method can be used to confirm ileo-colonic drug delivery in vivo. Caffeine serves as a release marker in this method, while sulfasalazine serves as a marker for colonic arrival. In this study, extrusion–spheronization was used to produce microcrystalline cellulose based pellets containing both caffeine and sulfasalazine. Dissolution tests revealed that a superdisintegrant, i.e., croscarmellose sodium or sodium starch glycolate, should be incorporated in the formulation to achieve acceptable release profiles for both sulfasalazine and caffeine. However, acceptable release profiles were only obtained when the pelletizing liquid consisted of ethanol/water 1/1 (v/v) but not with pure water. This phenomenon was ascribed to the differences in the degree of swelling of the superdisintegrant in the pelletizing liquid during the granulation process. The pellets were coated with the ColoPulse coating and showed the desired pH-dependent pulsatile release profile in vitro. In future clinical studies, ileo-colonic targeting should be verified.

Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen.

For many vaccines, multiple injections are required to confer protective immunity against targeted pathogens. These injections often consist of a primer administration followed by a booster administration of the vaccine a few weeks or months later. A single-injection vaccine formulation that provides for both administrations could greatly improve the convenience and vaccinee’s compliance. In this study, we developed parenterally injectable core-shell microspheres with a delayed pulsatile release profile that could serve as the booster in such a vaccine formulation. These microspheres contained bovine serum albumin (BSA) as the model antigen and poly(dl-lactide-co-glycolide) (PLGA) with various dl-lactide:glycolide monomer ratios as the shell material. Highly monodisperse particles with different particle characteristics were obtained using a microfluidic setup. All formulations exhibited a pulsatile in vitro release of BSA after an adjustable lag time. This lag time increased with the increasing lactide content of the polymer and ranged from 3 to 7 weeks. Shell thickness and bovine serum albumin loading had no effect on the release behavior, which could be ascribed to the degradation mechanism of the polymer, with bulk degradation being the main pathway. Co-injection of the core-shell microspheres together with a solution of the antigen that serves as the primer would allow for the desired biphasic release profile. Altogether, these findings show that injectable core-shell microspheres combined with a primer are a promising alternative for the current multiple-injection vaccines.

Oral colon delivery platform based on a novel combination approach: Design concept and preliminary evaluation

An oral colon delivery platform based on a novel combination strategy, leveraging multiple physiological characteristics of the intestine, is proposed. The system comprises a drug core, a water-swellable/soluble inner layer based on a hydrophilic cellulose derivative and an enteric outer layer (Eudragit® S) containing a microbially-degradable polysaccharide (high-amylose starch, Amylo N460), acting synergistically to prevent early release in the small intestine on the one hand, and release failure on the other. The Eudragit® S:Amylo N460 solid weight ratio in the external coating was 7:3; triethyl citrate and glyceryl monostearate were used as a plasticizer and an anti-tacking agent, respectively. The outer Eudragit® S/Amylo N460 layer was applied in a fluid bed using hydro-alcoholic or aqueous coating formulations. Two types of “inner” systems were studied: (i) Drug-loaded tablets coated with a low-viscosity hydroxypropyl methylcellulose (by aqueous spray-coating), and (ii) hydroxypropyl cellulose capsules prepared by injection-molding (filled with paracetamol as an analytical tracer). The obtained dosage forms were thoroughly characterized, including in vitro release measurements in various media. In all cases, pulsatile release profiles were obtained after medium change from 0.1 N HCl to phosphate buffer pH 7.4, with lag phases depending on the type and preparation technique of the hydrophilic polymer layer. The role of the microbiota on the release performance was explored in simulated colonic fluid (SCF), consisting in culture medium inoculated with fecal samples from inflammatory bowel disease patients. Clear differences in drug release were observed in SCF versus culture medium free of feces, indicating the effect of microbial degradation.

A REVIEW ON RECENT ADVANCEMENT IN PULSATILE DRUG DELIVERY SYSTEMS

Delivery systems with a pulsatile-release method are particularly involved in designing medicines for which traditional managed drug-release systems with the continuous release are not suitable. This medication also has a high first-pass impact or special conditions for chrono-pharmacology. These medications also have a high first-pass or unique chronopharmacological effect. The pulsatile release profile is characterised by a duration of no release (lag time) followed by a fast and full release of the drug. Pulsatile drug delivery systems may be classified into site-specific systems in which the drug is released inside the gastrointestinal system (e. g. colon) or time-controlled devices wherein the drug is released after a well-defined time period. Site-regulated release is typically controlled by environmental factors, such as pH or enzymes found in the intestinal tract, whereas drug release from time-controlled processes is controlled mainly by the delivery system and, preferably, not by the environment. This review covers various single-and multiple-unit oral pulsatile drug-delivery systems with an emphasis on time-controlled drug-release systems.

Polymer Nanocomposite Microactuators for On-Demand Chemical Release via High-Frequency Magnetic Field Excitation.

On-demand delivery of substances has been demonstrated for various applications in the fields of chemistry and biomedical engineering. Single-pulse release profile has been shown previously for micro/nanoparticles in different form factors. However, to obtain a sustained release, a pulsatile release profile is needed. Here, we demonstrate such a release profile from polymer magnetic nanocomposite microspheres loaded with chemicals. By exciting the microactuators with AC magnetic fields, we could achieve up to 61% cumulative release over a five-day period. One of the main advantages of using a magnetic stimulus is that the properties of the environment (e.g., transparency, density, and depth) in which the particles are located do not affect the performance. The operating magnitude of the magnetic field used in this work is safe and does not interact with any nonmetallic materials. The proposed approach can potentially be used in microchemistry, drug delivery, lab-on-chip, and microrobots for drug delivery.

Controlled transdermal drug delivery using a wireless magnetic microneedle patch: Preclinical device development

This paper presents a magnetic polymer-driven transdermal drug delivery system. Transdermal drug delivery has several advantages over oral and hypodermic administration, including painless delivery and avoiding first-pass metabolism. In this study, magnetic polymer composites (MPCs) and inductive sensing principles were utilized as the key actuator and sensor technologies to enable controlled drug release through a single hollow microneedle. The proposed system is capable of drug dispensing and dosage sensing, without the need for on-board electronics or batteries. Through experimental testing, the battery-less device demonstrated controllable zero-order and pulsatile drug release profiles, and was able to pierce and inject solution into excised human skin. This novel wireless pumping system provides the capability to control the volume dispensed for transdermal delivery in a compact, wearable form factor.

Controlled nanoparticle synthesis of Ag/Fe co-doped hydroxyapatite system for cancer cell treatment

Diagnosis of cancer by chemotherapy treatment, severe side effects caused by high dosages of cancer drugs include non-controlled cytotoxicity to bone marrow cells and immune cells. To overcome, we have synthesized nanoparticles with controlled sized hydroxyapatite (nHAp) materials doped and co-doped with silver and iron by co-precipitation, yielding materials that can treat both the infections and malignant tumors with non-cytotoxic nature to normal cells. Spherical and rod like morphologies were observed for the samples with higher Ag+ doping concentrations with average size of 50 ± 5 nm and (75 × 22) ± 5 nm2, whereas higher Ag+/Fe2+ co-doping concentrations yielded samples with spherical, rod-like, and flake-like structures. For samples nHAp and Ag+-nHAp samples were diamagnetic, whereas the Fe2+-nHAp and Ag+/Fe2+ co-doped samples were superparamagnetic. The in vitro biological toxicity study revealed that the Ag+/Fe2+-nHAp nanoparticles are effective for targeting to kill cancerous cells, for example, human cervical cancer (HeLa) cells efficiently while they are non-toxic to normal cells. Applying these nanoparticles for drug delivery system, 5-fluorouracil was loaded in the nanoparticles and studied its release kinetics. In the case of Ag+/Fe2+co-doped nHAp samples, a pulsatile drug release profile was observed, which the drug was released for about a week on varying the Ag+ and Fe2+ concentrations. The 5-fluorouracil release kinetics was well fitted by the first-order model with diffusion. Thus, nHAps co-doped with Ag+/Fe2+ material have the potential to lag the time on delivering the drug at site-specific could be with an application in biomedicine such as to treat malignant tumor without any bacterial side effect.

Ovalbumin-containing core-shell implants suitable to obtain a delayed IgG1 antibody response in support of a biphasic pulsatile release profile in mice.

A single-injection vaccine formulation that provides for both a prime and a boost immunization would have various advantages over a multiple-injection regime. For such a vaccine formulation, it is essential that the booster dose is released after a certain, preferably adjustable, lag time. In this study we investigated whether a core-shell based implant, containing ovalbumin as core material and poly(DL-lactic-co-glycolic acid) of various monomer ratios as shell material can be used to obtain such a booster release. An in vitro release study showed that the lag time after which the ovalbumin was released from the core-shell implant increased with increasing lactic to glycolic acid ratio of the polymer and ranged from 3–6 weeks. Fluorescence spectroscopy showed minimal differences between native ovalbumin and ovalbumin from core-shell implants that were incubated until just before the observed in vitro release. In addition, mice immunized with a subcutaneous inserted core-shell implant containing ovalbumin showed an ovalbumin-specific IgG1 antibody response after a lag time of 4 or 6–8 weeks. Moreover, delayed release of ovalbumin caused higher IgG1 antibody titers than conventional subcutaneous vaccination with ovalbumin dissolved in PBS. Collectively, these findings could contribute to the further development of a single-injection vaccine, making multiple injections of the vaccine superfluous.

PH-sensitive polymer nanocoating on hydrophilic composites fabricated using modified coaxial electrospraying

A modified coaxial electrospraying was developed to prepare structural polymeric nanocomposites, which was characterized by exploring a dilute solution without solidifiability through direct electrospraying as a shell fluid. With 0.5% (w/v) Eudragit L100 ethanol solution and a co-dissolving solution containing 10% (w/v) polyvinylpyrrolidone and 2% (w/v) diclofenac sodium (DS) in ethanol as shell and core fluids, respectively, medicated core-shell nanoparticles (NPs) were produced. These NPs had a diameter of 0.55 ± 0.09 μm and a homogeneous medicated core coated by a thin layer of ∼15 nm pH-sensitive polymer. Differential scanning calorimetric analyses verified that the NPs were amorphous nanocomposites. In vitro dissolution tests demonstrated that the core-shell NPs could provide a colon-targeted pulsatile drug release profile of the loaded DS through the synergistic action of the shell nanocoating and core hydrophilic nanocomposites. The protocols reported here pave a new way for developing novel structurally functional nanomaterials by expanding the applications of shell working fluids to untreated solutions.

Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites.

BackgroundColon-specific pulsatile drug release, as a combined drug controlled-release model, is a useful drug delivery manner for a series of diseases. New nanomedicines and related preparation methods are highly desired.MethodsWith diclofenac sodium (DS) as a model drug, a new type of structural nanocomposite (SC), in which composite polyvinylpyrrolidone (PVP)–DS core was coated by shellac, was fabricated via modified coaxial electrospinning. For comparison, traditional PVP–DS monolithic hydrophilic nanocomposites (HCs) were generated using a traditional blending process. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), water contact angle (WCA), and in vitro dissolution and ex vivo permeation tests were conducted to characterize the composites.ResultsSEM images demonstrated that both composites were linear nanofibers with smooth surface morphology and cross sections. TEM disclosed that the SCs had a thin shellac sheath layer of approximately 12 nm. XRD and ATR-FTIR results demonstrated that the crystalline DS was converted into amorphous composites with PVP because of favorable secondary interactions. WCA and in vitro dissolution tests demonstrated that the sheath shellac layers in SC could resist acid conditions and provide typical colon-specific pulsatile release, rather than a pulsatile release of HC under acid conditions. Ex vivo permeation results demonstrated that the SCs were able to furnish a tenfold drug permeation rate than the DS particles on the colon membrane.ConclusionA new SC with a shellac coating on hydrophilic amorphous nanocomposites could furnish a colon-specific pulsatile drug release profile. The modified coaxial process can be exploited as a useful tool to create nanocoatings.

Immunogenicity of pulsatile-release PLGA microspheres for single-injection vaccination

The World Health Organization's Expanded Programme on Immunization has led to a dramatic rise in worldwide vaccination rates over the past 40years, yet 19.4 million infants remain underimmunized each year. Many of these infants have received at least one vaccine dose but may remain unprotected because they did not receive subsequent booster doses due to logistical challenges. This study aimed to develop injectable controlled release microparticles with kinetics that mimic common vaccine dosing regimens consisting of large antigen doses administered periodically over the course of months in order to eliminate the need for boosters. Sixteen poly(lactic-co-glycolic acid) (PLGA) microsphere formulations containing bovine serum albumin (BSA) as a model vaccine antigen were screened in vitro to determine their respective release kinetics. Three formulations that exhibited desirable pulsatile release profiles were then selected for studying immunogenicity in mice. Two low-dose microsphere formulations induced peak anti-BSA IgG antibody titers of 13.9±1.3 and 13.7±2.2 log2 compared to 15.5±1.5 log2 for a series of three bolus injections delivered at 0, 4, and 8weeks with an equivalent cumulative dose. Similarly, high-dose formulations induced peak antibody titers that were 16.1±2.1 log2 compared to 17.7±2.2 log2 for controls. All three microparticle formulations studied in vivo induced peak antibody titers that were statistically similar to bolus controls. These results suggest that pulsatile antigen release from polymeric microparticles is a promising approach for single-injection vaccination, which could potentially reduce the logistical burden associated with immunization in the developing world.

Acrylic hydrogels containing MET-loaded poly(acrylic acid-co-methyl methacrylate) micro- and nanoparticles

Acrylic hydrogels containing metronidazole (MET)-loaded poly(acrylic acid-co-methyl methacrylate) (PAM) micro- and nanoparticles were prepared. The size distributions of the PAM micro- and nanoparticles and the MET-loaded PAM micro- and nanoparticles were determined by dynamic light scattering (DLS), and particle microstructure was characterized using wide-angle X-ray diffraction (WAXD). Hydrogel structure was examined using FTIR-ATR spectroscopy and surface morphology was characterized using scanning electron microscopy, with elemental analysis performed at particular points and on the surface (SEM-EDS). The resulting composite hydrogels were studied in terms of their swelling behavior and biological properties in water and simulated body fluid (SBF and Ringer’s solution). In addition, the drug release behavior of the hydrogels was evaluated in water and phosphate-buffered saline (PBS) at 37 °C. The acrylic hydrogels containing MET-loaded PAM micro- and nanoparticles showed pulsatile MET release profiles that could prove beneficial in wound treatment, as they would allow controlled regeneration of tissue under healing conditions.

Near-infrared light responsive multi-compartmental hydrogel particles synthesized through droplets assembly induced by superhydrophobic surface.

Light-responsive hydrogel particles with multi-compartmental structure are useful for applications in microreactors, drug delivery and tissue engineering because of their remotely-triggerable releasing ability and combinational functionalities. The current methods of synthesizing multi-compartmental hydrogel particles typically involve multi-step interrupted gelation of polysaccharides or complicated microfluidic procedures with limited throughput. In this study, a two-step sequential gelation process is developed to produce agarose/alginate double network multi-compartmental hydrogel particles using droplets assemblies induced by superhydrophobic surface as templates. The agarose/alginate double network multi-compartmental hydrogel particles can be formed with diverse hierarchical structures showing combinational functionalities. The synthesized hydrogel particles, when loaded with polypyrrole (PPy) nanoparticles that act as photothermal nanotransducers, are demonstrated to function as near-infrared (NIR) light triggerable and deformation-free hydrogel materials. Periodic NIR laser switching is applied to stimulate these hydrogel particles, and pulsatile release profiles are collected. Compared with massive reagents released from single-compartmental hydrogel particles, more regulated release profiles of the multi-compartmental hydrogel particles are observed.

Development and evaluation of nifidipine loaded tablet formulation for colon drug delivery

Pulsatile release profile is characterized by a lag time followed by rapid and complete drug release. Pulsatile drug delivery systems are classified into time-controlled and site-specific delivery systems. The lag time is taken as the time of less than 10% drug release. The objective of present study was to develop a pulsatile compression coated tablet. The system was developed into two steps i.e. firstly core tablet was prepared containing Nifidipine; secondly core tablet was coated with polymer blend of ethyl cellulose (water insoluble polymer) and Eudragit L 100 (Enteric polymer). From the study it was concluded that the formulation having a coating level of 50% w/w of core and weight ratio of ethyl cellulose to Eudragit L 100 (20%) showed lesser release profile as compared to other formulation i.e. 52.83% in 12hrs. As we increase the weight ratio of ethyl cellulose to Eudragit L 100 better entrapment of drug leading to controlled release of drug.