Compression Coat Research Articles

Alleviating the Influence of Circadian Rhythms and Drug Properties to the Release of Paliperidone Gel Matrix Tablets with Compression Coating Technology and Microenvironment Shaping

The influence of circadian rhythms is an important content in oral dosage form study which is shown as different pH conditions and gastrointestinal dynamics in the gastrointestinal tract. The purpose of this study was to alleviate the influence of circadian rhythms and drug properties to the release of gel matrix tablets in vitro and in vivo. In this study, the compression coating technology and microenvironment shaping were utilized to achieve the alleviation of the influence of circadian rhythms and drug properties. The compression coating technology was used to alleviate the influence of gastrointestinal dynamics, and microenvironment shaping was used to alleviate the interference of different pH condition variations. The self-made compression coating tablet could maintain a consistent release rate in different pH conditions and different dynamic environments in vitro for 24 h. In vivo, the pharmacokinetic parameters Cmax and Tmax were 3701.675 ng/mL and 24 h, respectively, and the release effect in vivo was similar to the paliperidone osmotic pump tablet with the ability to alleviate the influence of circadian rhythms. The correlation coefficient R2 was 0.9914 for the self-made paliperidone compression coating tablet in vitro-in vivo correlation. The interference caused by circadian rhythms was alleviated so that the compression coating technology with microenvironment shaping could replace the osmotic pump technology with easier preparation process and cheaper costs in vitro and in vivo and achieve the effect of alleviating the interference of circadian rhythms.

Compression Coating Technique and its Formulation in Circadian Rhythm Activity with Chronotherapeutic Drug Delivery System

Background: Circadian rhythms is a natural process that regulates the sleep wake cycle which is associated with several physiological, biochemical, endocrine, behavioural processes in humans and entrainment to light-dark cycle. The activity of Ramelteon is believed to contribute to its sleep-promoting properties and thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle. A tablet can be given before 2 hr of bed time, so the Ramelteon drug shows its effect throughout the night by releasing the active content with lag time followed by sustained action to promote the sleep. Materials and Methods: Chronotherapeutic drug delivery system were prepared by compression coating technology using pH independent, hydrophilic and hydrophobic polymers. Results: Drug excipient compatibility indicated that the Ramelteon Active pharmaceutical ingredient (API) is compatibility with the excipients proposed. The X-ray Diffraction (XRD) studies indicated that the crystalline form of the Ramelteon API existed in the finished formulation. Conclusion: The core tablets containing Eudragit RSPO 10mg/tablet and ratio of Ethyl cellulose: Hydroxy propyl methyl cellulose (HPMC) of 70:30 in the outer coating material yielded a desired lag time of 2 hr and drug release for a period of 4 hr to achieve a chronotherapeutic drug delivery system. Ramelteon is an excellent candidate in designing chronotherapeutic drug delivery systems and further in vivo studies can be explored in the treatment of circadian rhythm with sleep wake cycle disorders.

Formulation and Evaluation of Ciprofloxacin Colon Targeted Tablets By Compression Coating Technique Using Guar Gum and Hydroxypropyl Methylcellulose

Formulation and Evaluation of Ciprofloxacin Colon Targeted Tablets By Compression Coating Technique Using Guar Gum and Hydroxypropyl Methylcellulose

Preparation and Evaluation of Zafirlukast Compression Coated Tablets for Chronotherapeutic Drug Delivery

The objective of the present study was to formulate and evaluate an oral, time-controlled drug delivery system of Zafirlukast. Zafirlukast belongs to BCS class II drugs as it has poor aqueous solubility and good permeability. Hence an attempt has been made to improve its aqueous solubility by solid dispersion technique so that its dissolution, bioavailability, and therapeutic effect can be optimized. The optimized solid dispersion was then formulated into a chronotherapeutic drug delivery system by compression coating technology. FT-IR study revealed that there was no chemical interaction between the drug and polymers used. Tablets were prepared by direct compression method using different super disintegrants and then followed by compression coating using natural polymers. Pre-compression and post-compression parameters complied with the Pharmacopoeia limit for the tablets. In vitro release studies were performed and the results indicated the formulation Z9F9 to be the optimized formulation.

Synthesis and Characterization of Carboxymethylated Locust Bean Gum for Developing Compression Coated Mucoadhesive Tablets of Cinnarizine

Carboxymethylated locust bean gum (CLBG) was synthesized by carboxymethylation of locust bean gum (LBG) using monochloroacetic acid followed by characterization involving SEM, XRD and FTIR techniques. The CLBG exhibited changes in the surface morphology along with relative amorphous nature as indicated in SEM and XRD analysis, respectively. In SEM images, locust bean gum (LBG) exhibited irregular particle with smooth surface morphologies whereas CLBG depicted surface roughness with relatively irregular edges. XRD study indicated relative amorphous nature of CLBG. The modified gum was employed for developing compression coated tablets of cinnarizine. The core tablets coated with CLBG exhibited mucoadhesive detachment force of 11.44 ± 2.09 to 16.07 ± 1.88 N compared to 4.10 ± 0.95 to 5.52 ± 1.13 N of locust bean gum coated tablets. The CLBG depicted better sustained drug release behaviour when compared with the pure gum. In conclusion CLBG is a suitable polymer candidate for developing mucoadhesive drug delivery systems with controlled release property.

Development and Evaluation of Mucoadhesive Tablets of Cinnarizine Using Carboxymethylated Guar Gum by Compression Coating Technique

The e study was designed to perform carboxymethylation of guar gum and to develop mucoadhesive tablets of cinnarizine by compression coating technology. Carboxymethyl guar gum was synthesized and characterized by FTIR, SEM, XRD and DSC techniques. Inner core tablets of cinnarizine were compression coated with guar gum and carboxymethylated guar gum. The formulated mucoadhesive tablets were evaluated for various tablet parametric tests viz. hardness, friability, content uniformity, thickness. Ex vivo mucoadhesion strength and in vitro drug release studies were also conducted. Appearance of new FTIR peaks, surface morphology analysis by SEM, reduction in crystallinity by XRD and appearance of the endothermic peak in DSC thermogram point out towards successful carboxymethylation of guar gum. Mucoadhesive strength of F1CGG to F4CGG batches of mucoadhesive tablets prepared with carboxymethyl guar gum found higher than F1GG to F4GG batches of tablets prepared with guar gum. Carboxymethyl guar gum exhibited sustained release effect on in vitro release cinnarizine from compression coated mucoadhesive tablets. The study confirms that carboxymethylation of guar gum improves the mucoadhesive properties of pure guar gum. Also, the compression coating of carboxymethylated guar gum enhances the gastric retention time and sustained release of cinnarizine. Carboxymethyl guar gum can be used as mucoadhesive polymer for developing different mucoadhesive drug delivery systems.

Desirability Based Optimization of New Mesalazine Modified Release Formulations: Compression Coated Tablets and Mini Tablets in Capsules

Background: Mesalazine (5-aminosalicylic acid, 5-ASA) is a drug substance with an antiinflammatory activity, which is mainly used in the symptomatic treatment of diseases, such as Ulcerative Colitis, the Crohn's disease and the idiopathic inflammatory bowel disease. Mesalazine exerts its effect locally in the inflamed area of the intestine and not through systematic absorption, therefore the investigation of its release characteristics from solid pharmaceutical formulations is of great importance. Objective: The development of novel mesalazine modified release formulations with improved properties, regarding drug release in the gastrointestinal tract, by utilisation of the Design of Experiments (DoE) approach. Methods: D-optimal experimental design was applied. A Simplex Lattice mixture design was used for the development of suitable capsules containing 4 mini tablets and a D-optimal mixture design was used for compression-coated tablets, with the following characteristics: ≤10% release in 2 h, to minimize its degradation in the upper gastrointestinal tract, 20-40% release in 5 h for mesalazine administration in the small intestine, and quantitative release in 12 h for colonic delivery. The dissolution experiments were conducted in gastrointestinal-like fluids and pectinases to simulate the pectinolytic enzymes present in the colon. Results: The optimal compositions were reached via the desirability function, as a compromise to the different responses. The optimal solutions for both formulations led to colon-specific delivery of the active substance with minimal 5-ASA release in the upper gastrointestinal tract and appeared to conform with the pre-determined characteristics. Hard gelatin capsules, when filled with mini-tablets led to the aimed modified release profile, having sigmoidal characteristics and compression coated tablets led to colonic delivery. Conclusion: Two novel mesalazine formulations were developed with the desirable colonic release, by conducting a minimal number of experiments, as suggested by DoE experimental design.

Effect of polymer concentration and solution pH on viscosity affecting integrity of a polysaccharide coat of compression coated tablets

Tablets, compression coated with certain polysaccharides and intended for colon delivery, retain the integrity of the coat for an initial period of about 6 h (lag period) beyond which (post-lag period) the coat is degraded by colonic enzymes to induce drug release. This work was undertaken to investigate the factors which influence the integrity of the coat during the lag period. Core tablets containing two model drugs were compression coated with various amounts of carboxymethyl locust bean gum (CMLBG). In-vitro release of drugs, erosion of coat, and steady shear viscosity of CMLBG solutions having different concentrations and solution pH were determined. The viscosity of CMLBG that depended primarily on CMLBG concentration and partly on solution pH was responsible for erosion and integrity of the coat in the lag period. Evaluation of polymer viscosity could describe the integrity of coat of a polysaccharide coated tablet in the lag period.

Nifedipine di-matrix depot tablets prepared by compression coating for obtaining zero-order release

Compression coating is a possible process for obtaining zero-order release. Nifedipine compression-coated (CC) di-matrix depot tablets were prepared from a single punch tablet press with low viscosity hydroxypropyl cellulose (HPC-L) as the inner polymer, and with middle viscosity hydroxypropyl cellulose (HPC-M), HPC-L and Eudragit RSPO as outer polymers. The release behavior and mechanisms in vitro of the final tablets were investigated, and gravimetric analysis was used to study the release mechanism. The fast release of the core depot and slow release of the outer depot with time formed total zero-order release. The results showed that the formulation presented ideal zero-order release at the weight ratio of nifedipine 3:5 (core: layer), the combination of HPC-L and HPC-M (56:25) in the outer depot, and with the core depot placed in the center. The CC tablets released to more than 95% in 24 h and fitted a zero-order model with the equation Mt/M∞ = 0.038t (R2 = 0.98555). In conclusion, zero-order release of nifedipine over 24 h could be achieved by applying polymer HPC-L and HPC-M with the compression coating technique.

Tablets of paliperidone using compression-coated technology for controlled ascending release

The aim of this work was to prepare ascending release compression-coated (CC) tablets with paliperidone (PAL) using a simple manufacturing technique and short manufacturing process. The release behavior and mechanisms in vitro of the final tablets was investigated and evaluated. The PAL CC tablets were comprised of a core layer of high viscosity hydroxypropyl cellulose (HPC-H) and a coating layer of high viscosity hydroxypropyl methylcellulose (HPMC-K100M). Several factors such as materials and core tablet compositions were studied for their influence in the formulation procedure. The drug release mechanism was studied using gravimetric analysis. The data could be fitted to the Peppas model. The ascending drug release results were expressed in terms of the slope of the release curve at different time points. Results showed that the formulation could achieve a good ascending drug release when the weight ratio of PAL was 5:1 (core:layer). The fraction of HPC and HPMC was 33 %, and the combination of Eudragit RL-PO was 10%. The ascending release mechanism was due to solvent penetration into the PAL CC tablets, and subsequent drug dissolution from the gelatinous HPC and HPMC matrix erosion. The release mechanism was therefore a combination of diffusion and erosion. This work demonstrated that the compression-coated tablets could achieve controlled ascending release over 24 h for the oral administration systems.

Quality by Design Empowered Development and Optimisation of Time-Controlled Pulsatile Release Platform Formulation Employing Compression Coating Technology.

The research was envisaged for development of time-controlled pulsatile release (PR) platform formulation to facilitate management of early morning chronological attacks. The development was started using prednisone as a model drug wherein core tablets were prepared using direct compression method and subsequently compression-coated with ethylcellulose (EC)-hydroxypropyl methylcellulose (HPMC) excipient blend. Initially, quality target product profile was established and risk assessment was performed using failure mode and effect analysis. In an endeavour to accomplish the objective, central composite design was employed as a design of experiment (DoE) tool. Optimised compression-coated tablet (CCT) exhibited 4-6h lag time followed by burst release profile under variegated dissolution conditions viz. multi-media, change in apparatus/agitation and biorelevant media. Afterwards, five different drugs, i.e. methylprednisolone, diclofenac sodium, diltiazem hydrochloride, nifedipine and lornoxicam, were one-by-one incorporated into the optimised prednisone formula with replacement of former drug. Change in drug precipitated the issues like poor solubility and flow property which were respectively resolved through formulation of solid dispersion and preparation of active pharmaceutical ingredient (API) granules. Albeit, all drug CCTs exhibited desired release profile similar to prednisone CCTs. In nutshell, tour de force of research epitomised the objective of incorporating diverse drug molecules and penultimately obtaining robust release profile at varying dissolution conditions.

Compression-Coated Tablet for Colon Targeting: Impact of Coating and Core Materials on Drug Release.

This work was envisaged to develop compression-coated tablets using a blend of Ca(+2) ion cross-linked carboxymethyl xanthan gum (CMXG) and sodium alginate (SAL) for delayed release of immediate pulse release tablets of prednisolone (PDL) in the colon without the need of colonic bacterial intervention for degradation of the polysaccharide coat. The core tablets containing PDL and other compatible excipients were prepared by direct compression method and subsequently compression coated with different ratios of CMXG and SAL. Long T lag, the time required to restrict the drug release below 10%, and short T rap, the time required for immediate release following the T lag, were considered as suitable release parameters for evaluation of colon targeting of PDL tablets. Among the various compression coats, a blend of CMXG and SAL in a ratio of 1.5:3.5 provided T lag of 5.12 ± 0.09 h and T rap of 6.50 ± 0.05 h. The increase in microcrystalline cellulose (MCC) and crospovidone (CP) in the core tablets did not change T lag significantly although decreased the T rap marginally. Inclusion of an osmogen in the core tablets decreased the T lag to 4.05 ± 0.08 h and T rap to 3.56 ± 0.06 h. The increase in coat weight to 225 mg provided a reasonably long T lag (6.06 ± 0.09 h) and short T rap (4.36 ± 0.20 h). Drug release from most of the formulations followed the Hixson-Crowell equation and sigmoidal pattern as confirmed by the Weibull equation. In conclusion, tablets, compression coated with CMXG and SAL in a ratio of 1.5:3.5 and having 225-mg coat weight, were apparently found suitable for colon targeting.

Colon-specific double-compression coated pulsatile tablets of ketorolac tromethamine: Formulation development and pharmacokinetics

In the recent pharmaceutical research, pulsatile drug delivery has been of interest to achieve improved drug therapies. The present study is aimed to formulate and study the pharmacokinetics of colon-specific pulsatile ketorolac tromethamine tablets using double-compression coating method. In this, inner compression coat made of sodium starch glycolate as swelling layer and outer compression coat (release controlling layer) contains sodium alginate and hydroxypropyl methylcellulose K 15M. From the in vitro drug release studies, F5 tablets showed 5.02 ± 0.16% drug release in 5 h and it was progressively expanded to 99.78 ± 0.64% in 24 h that demonstrate the colon-specific drug release. From the stability studies, F5 formulation showed the good stability and it was proved by calculating the similarity factor i.e., 83.92. From the pharmacokinetic evaluation, immediate release core tablets producing peak plasma concentration (Cmax) was 4425.23 ng/ml at 2 h Tmax and colon-specific double-compression coated tablets demonstrated Cmax = 3456.47 ng/ml at 10 h Tmax. The area under curve values for the core and double-compression coated tablets were 10128.53 and 17467.62 ng-h/ml respectively and the mean resident time was 4.21 h and 10.34 h respectively. In conclusion, development of ketorolac tromethamine double-compression coated pulsatile tablets is a promising way to achieve colon-specificity.

Formulation and pharmacokinetics of colon-specific double-compression coated mini-tablets: Chronopharmaceutical delivery of ketorolac tromethamine

The present study is designed and significantly planned to study the effect of double-compression coating on core mini-tablets to attain the chronopharmaceutical delivery of ketorolac tromethamine to colon. Double-compression coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. From the in vitro drug release studies, F6 tablets was considered as the optimized formulation, which retarded the drug release in stomach and small intestine (3.51±0.15% in 5h) and progressively released to colon (99.82±0.69% in 24h). The release process followed supercase-II transport with zero order release kinetics. Similarity factor calculated from stability studies was found to be 84.73. From the pharmacokinetic evaluation, the immediate release core mini-tablets reached peak plasma concentration (Cmax of 4532.68±28.14ng/ml) at 2h Tmax and colon targeted tablets showed Cmax=3782.29±17.83ng/ml at 12h Tmax. The area under the curve and mean resident time of core mini-tablets were found to be 11,278.26±132.67ng-h/ml and 3.68h respectively while 17,324.48±56.32ng-h/ml and 10.39h for compression coated tablets. Hence the development of double-compression coated tablets is a promising way to gain the chronopharmaceutical delivery of ketorolac tromethamine to colon.

A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

MICROBIAL TRIGGERED COLON TARGETED COMPRESSION COATED TABLETS OF TENOXICAM: FORMULATION AND EVALUATION

The present investigation deals with to formulation and evaluation of colon specific drug delivery system of Tanoxicam by compression coated tablet technique. Tenoxicam, Avicel pH101, HPMC K4M, Guar gum were used as components.Tenoxicam compression coated tablets were prepared and evaluated for differential scanning colorimetry (DSC), FTIR spectroscopy and in-vitro dissolution study without rat caecal content and with rat caecal content. The results suggest that Colon specific drug delivery system of Tenoxicam compression coated tablets were formulated successfully by using natural polymer such as Guar gum in combination with different concentration of HPMC. Tablets were evaluated for drug content, hardness, thickness, friability, weight variation, in-vitro dissolution and all the results were found within the specification. As the concentration of HPMC in compression coat increased, drug release was decreased. Based on in-vitro drug release study, it was concluded that compression coated tablets with combination of 90% Guar gum and 10% HPMC could produce a successful drug targeting to the colon with minimal amount released in the stomach and small intestine for tenoxicam.

Study on the Effect of HPMC on Compression Coated Floating Pulsatile Delivery of Bisoprolol

The present work aimed to develop and study the effect of HPMC on compression-coated floating - pulsatile delivery of Bisoprolol. Inner core tablet contains bisoprolol and a super disintegrant. Outer shell contains HPMC K4M and HPMC K100M as erodible layer along with a gas generating agent. Compression-coated tablet of bisoprolol with 120mg HPMC K4M (B2) showed a lag time of 3.40±0.1 hrs with 99.81% drug release. Whereas 110mg HPMC K100M (B5) showed a lag period 4.0±0.1 hrs with 98.91% drug release. A 32 factorial design was applied. HPMC K4M CR and K100M were independent variables whereas drug release, lag time at 4 hrs and swelling index were dependent variables. To understand the interaction of independent variables on dependent variables three dimensional surface response plots were drawn. The responses exhibited by batch F4 (55 mg HPMC K4M and 65 mg K100M) showed lag time 4.20 hrs following the sigmoidal release pattern. Optimized batch F4 gave good in-vitro in -vivo correlation. Keywords: Bisoprolol, compression, floating tablet, HPMC, lag time, pulsatile drug delivery system.

An in situ crosslinked compression coat comprised of pectin and calcium chloride for colon-specific delivery of indomethacin

The use of pectin for colon-specific drug delivery has been extensively investigated; however, when used alone, pectin is often compromised due to its high solubility. This study explored the feasibility of using an in situ compression-coated crosslinking system, composed of pectin and calcium chloride, for colon-specific drug delivery. A pectin/calcium chloride (P/Ca) coating was compressed onto a core tablet. The colon specificity of the compression-coated tablet was verified by dissolution, pharmacokinetics and scintigraphy with 99mTc labeling. The in situ pectin and calcium chloride gel slowed the release of indomethacin. The lag time varied between 3 h and 7 h depending on the amount of calcium chloride and the coating weight. Pectinase triggered the release of indomethacin from the compression-coated tablet, which was then accelerated by the calcium chloride in the coating layer. The compression-coated tablet had a prolonged tmax and apparent t1/2, as well as a decreased Cmax and AUC0–t, compared with the core tablet counterpart. Evaluation with γ-scintigraphy verified colon-specific delivery of the compression-coated tablet. In conclusion, the P/Ca in situ crosslinking system worked well for colon-specific drug delivery.

Effects of Compression and Filler Particle Coating on the Electrical Conductivity of Thermoplastic Elastomer Composites

Elastomeric polymers can be filled with metallic micro- or nanoparticles to obtain electrical conductivity, in which the conductivity is largely determined by the intrinsic conductivity of and contact resistance between the particles. Electrons will flow through the material effectively when the percolation threshold for near-neighbor contacts is exceeded and sufficiently close contacts between the filler particles are realized for electron tunneling to occur. Silver-coated glass microparticles of two types (fibers and spheres) were used as fillers in a thermoplastic elastomer composite based on styrene–ethylene–butylene–styrene copolymer, and the direct-current (DC) resistance and radiofrequency impedance were significantly reduced by coating the filler particles with octadecylmercaptan. Not only was the resistance reduced but also the atypical positive piezoresistivity effect observed in these elastomers was strongly reduced, such that resistivity values below 0.01 Ω cm were obtained for compression ratios up to 20%. In the DC measurements, an additional decrease of resistivity was obtained by inclusion of π-extended aromatic compounds, such as diphenylhexatriene. Some qualitative theories are presented to illuminate the possible mechanisms of action of these surface coatings on the piezoresistivity.

Characterization of critical physical and mechanical properties of freeze-dried grape powder for development of a clinical patient delivery system

Grapes are hypothesized to be a “food medicine.” Freeze-dried grape powder (FDGP) is being used to test clinical activity for a variety of applications and a reproducible and reliable delivery system was required. The FDGP was characterized using traditional physico-chemical methods to generate the data needed to identify its primary liability, i.e. moisture sorption. Above a threshold level of moisture content (~25% w/w, at RT), the material becomes both difficult to handle and exhibits significant degradation of several potentially clinically important chemical components (catechin, epicatechin, resveratrol). A moisture sorption isotherm was then used to tie the threshold to the exposure relative humidity above which this occurs. Kinetic uptake studies were used to estimate the maximum safe exposure time at a given humidity (a square root time dependence of moisture uptake was observed). Armed with this knowledge, a FDGP compact coated with a compression coat [100% bees wax or combinations of carnauba wax (70%) with HPC (30%) or Avicel® PH 102 (30%) or lactose monohydrate (30%)] was developed that will insure the shelf life of the material without the need for special handling for approximately more than 3 months.