Formulation Of Matrix Tablets Research Articles

New Hydrophilic Matrix Tablets for the Controlled Released of Chlorzoxazone.

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % Kollidon®SR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.

Modified Release of Acetaminophen from Matrix Tablet Formulations: Influence of Tablet Geometry

Background: Acetaminophen (APAP) or paracetamol is a widely used over-the-counter, analgesic (common conditions treated include headaches, backache, toothache, muscle aches, arthritis, sore throat etc.) and antipyretic drug. It can be administered orally, in the form of a tablet (plain, effervescent, orodispersable, etc.) or liquid, rectally in the form of a suppository or by injection (intravenously or intramuscularly). It is well absorbed orally with a plasma elimination half-life ranging from 1 to 4 h. The modified release oral formulation can prolong its therapeutic effects by maintaining APAP average plasma concentrations. Objective: In the context of this work, two APAP formulation tablets with different geometries were produced from standard pharmaceutical excipients to investigate the role of altered tablet geometry in modified oral drug delivery. Methods: APAP tablets were prepared by direct compression, using hydroxypropyl methylcellulose (HPMC K15M), polyvinylpyrrolidone (PVP, MW: 55,000) and magnesium stearate, as ingredients. The release profiles were probed in aqueous dissolution media (pH 1.2 and 6.8) to simulate the conditions in the gastrointestinal tract in a United States Pharmacopeia (USP) dissolution paddle apparatus II and analyzed using an ultraviolet (UV) spectrophotometer (λmax = 244 nm). Results: The results indicated that the tablets were within the acceptable range of all evaluation parameters (tablet dimensions, drug content, weight variation, and breaking force) as defined by the international standards stated in the US Pharmacopoeia. The dissolution results showed that the APAP’s release profile was controlled by the tablets’ different geometries and, specifically the surface area (SA) and the surface area/volume (SA/V) ratio of the different tablets. The tablets with smaller SA/V ratios and SA showed slower drug release, indicative of a modified release motif. Conclusion: Altered tablet geometry plays an important role in APAP-modified oral drug delivery.

Potentials of Sterculia tragacantha Lindl seed husk gum as a release modifier in matrix tablet formulation

Natural gums have been utilized severally in the design of matrix tablets, either in their native or modified forms. The primary objective of this work was the extraction, characterization and utilization of the seed husk gum from Sterculia tragacantha Lindl as a release modifier in theophylline matrix tablets. Gum was extracted from the fresh seed husk of Sterculia tragacantha and tablet formulated via wet granulation. Drug-polymer compatibility was determined by FTIR and DSC while formulated tablets were evaluated for their in vitro dissolution release profile in two media, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) and compared with a commercial brand. Extracted gum powder presented a poor flow which improved on granulation, had a better swelling index and water holding capacity than tragacanth gum. Formulated tablets passed standard tablets test and sustained theophylline release up to 90.97 % and 88.09 % in SGF and SIF respectively at the twelfth hour. Drug release kinetics was by zero order in SGF via non-fickian diffusion. S. tragacantha seed husk gum presented a promising potential as a release retarding agent.

Formulation and Evaluation of Sustained Release Matrix Tablet of Valsartan

The aim of this study was to develop antihypertensive matrix tablets with sustained release of valsartan, an angiotensin type II receptor antagonist, using hydroxypropyl methylcellulose and combination of ethyl cellulose material as matrix in different proportions by wet granulation. The granules are evaluated by tapped density, bulk density, angle of repose and compressibility index. The tablets are tested for friability, hardness, weight variation and in vitro release. The granules showed good flow properties and compressibility properties and all tablet formulations showed pharmaceutical properties. The result of dissolution study indicate that the formulation prepared by combination of high grade HPMC K100M and ethyl cellulose showed maximum drug release for 12hrs and high drug release around 98.56% i.e., Formulation F8 is the best formulation.

Formulation and Evaluation of Miglitol Sustained Release Matrix Tablets Using Moringa Oleifera Gum

Formulation and Evaluation of Miglitol Sustained Release Matrix Tablets Using Moringa Oleifera Gum

Evaluation of Cassia fistula seed galactomannan as tablet-binder in formulation of diclofenac sodium-loaded monolithic matrix tablet

The present study aimed to evaluate Cassia fistula seed galactomannan (CFSG) as a tablet-binder in the formulation of a monolithic matrix tablet using diclofenac sodium as a model drug. Initially, CFSG was extracted and purified from the seeds of the Cassia fistula tree and then screened for phytochemicals. Native CFSG was characterized with polysaccharide content determination, monosaccharide composition analysis, elemental analysis, FTIR, solid-state 13C NMR, molecular weight, zeta potential, DSC, TGA-DTA, XRD, viscosity, pH and surface tension, rheology, SEM and acute oral toxicity study. Prior to formulation, the drug-CFSG compatibility was checked by FTIR, DSC, and XRD. Diclofenac sodium-loaded granules were prepared by the wet granulation method and evaluated for various granule properties. Finally, granules were compressed into tablets and evaluated for binding and other tablet properties. The granules showed to have optimum micromeritic properties. Tablet hardness and friability were found to be approximately 7 kg/m2 and 0.3 %, respectively, which substantiate the excellent binding capacity of CFSG. Other tablet properties were also found to be within the Pharmacopoeial compliance limit. The tablets with a minimum concentration of CFSG (2.5%w/w) as binder showed appreciable mechanical strength and faster drug release, which ratifies CFSG as an alternative tablet binder.

Formulation and Evaluation of Propranolol Hydrochloride Sustained Release Matrix Tablets Using Different Grades of HPMC and MCC

Formulation and Evaluation of Propranolol Hydrochloride Sustained Release Matrix Tablets Using Different Grades of HPMC and MCC

Formulation and Optimization of Matrix Tablets Based on Spirulina and Vitamin C

Spirulina is a type of algae widely consumed around the world as a dietary supplement due to its great nutritional potential. However, it does not contain vitamin C, a vital vitamin for the proper functioning of the human body, particularly given its immunostimulant potential. The objective of this work was to formulate sustained release spirulina–vitamin C matrix tablets that would enhance particularly a prolonged release and better absorption of vitamin C. A galenic formula based only on vitamin C was made, and then the proportion of vitamin C was reduced in favor of spirulina powder. The manufactured tablets were then subjected to various pharmacopeial quality control tests. The results of these tests showed a good distribution of the powder mixtures in the formulated tablets (i.e., mass uniformity test) and satisfactory outcomes were found for the content uniformity, disintegration and dissolution tests (with 45 % of vitamin C dissolved after 4 hours). Only the results for the friability test were unsatisfactory, indicating the need to improve the physical properties of the powders before compression. These findings open a new area for developing supplementary dietary. 
 Keywords: Spirulina, Vitamin C, Matrix tablet, Quality control.

Formulation and Evaluation of Cola acuminata Gum-based Mucoadhesive Sustained-release Matrix Tablets of Diclofenac Sodium.

This study aimed to evaluate Cola acuminata gum (CAG) for the formulation of mucoadhesive sustained-release matrix tablets of diclofenac sodium. Different batches of granules containing CAG and 100 mg of DS in ratios 0.5:1, 1:1, 2:1, and 3:1 were prepared, compressed into tablets, and evaluated for mucoadhesive strength, swelling index, and drug release in SGF (pH 1.2) and SIF (pH 7.4). Swelling indices and mucoadhesive strengths of the tablets were pH-dependent. Swelling indices of 56 ± 2.03 to 121 ± 2.19% and mucoadhesive strengths of 7.25 ± 1.45 to 15.43 ± 2.71 g/cm2 obtained at pH 7.4 were significantly higher (p<0.05) than swelling indices of 25 ± 2.43 to 47 ± 3.15% and mucoadhesive strengths of 5.52 ± 0.76 to 9.22 ± 1.95 g/cm2 obtained at pH 1.2. The percentage release of DS from the matrix tablets at pH 1.2 after 2 h (T2h) was insignificant. However, the percentage of drug release at pH 7.4 was significant for all the batches and dependent on the CAG concentration. The drug release was in the order of batches containing 3 g (80.44 ± 7.75) < 2 g (86.35 ± 5.65) < 1 g (90.08 ± 6.14) < 0.5 g (99.70 ± 3.90). The time for maximum drug release was 7 h (T7h) for CAG containing 0.5 g and 10 h (T10h) for other batches. This study showed that CAG could be useful for mucoadhesive sustained drug delivery.

In vivo Evaluation for the Anticoagulant Activity of Dipyridamole Matrix Tablets

Dipyridamole (DYP) is potent drug that prevents the thromboembolic risk. It has been clinically used for chronic treatment of angina pectoris treatment and during the valve replacement. heart valve replacement and long-term angina pectoris treatment and is well absorbed in the stomach with BCS class II drug and low oral bioavailability. The present research investigation was focused on the formulation of matrix tablets of Dipyridamole cocrystals and the evaluation of In vivo anticoagulant activity. The results of the study showed that the formulated matrix tablets of dipyridamole cocrystals showed improved efficacy in comparison with the plain drug by enhancing the pre-compression parameters such as bulk density, tap density, Carr's index, angle of repose and Hausner's ratio and post-compression parameters like thickness and weight variation, hardness and friability, In vitro dissolution parameters. The improved efficacy was confirmed by improvement in the pharmacodynamic parameters such as cutaneous bleeding time and clotting time indicative of enhanced bioavailability of dipyridamole. Thus, it can be concluded that the dipyridamole matrix tablets prove to be more effective in producing the anticoagulant effect in clinical practice as compared to the plain drug resulting in more patient compliance.

Formulation, Evaluation and Comparison of Sustained Release Matrix Tablet of Losartan Potassium Using Natural Polymers

Formulation, Evaluation and Comparison of Sustained Release Matrix Tablet of Losartan Potassium Using Natural Polymers

Influence of pH on the release of a once daily formulation of ciprofloxacin tablets prepared with different polymers

Purpose: To study the release behaviour of ciprofloxacin hydrochloride tablet matrices prepared with different polymers in dissolution media of different pH. Methods: Different formulations of slow-release matrix tablets of ciprofloxacin hydrochloride were prepared with polymers, namely, ethyl cellulose (Etc), hydroxyethyl cellulose (Hec), hydroxypropyl methylcellulose (Hpc), and Eudragit® L-100 (Eud) using matrix embedding technique. The matrix tablets were characterized and studies of their dissolution profiles were studied in 0.1 N HCl (pH 1.2) and in simulated intestinal fluid (excluding enzymes) of pH 4.0, 6.0, and 7.4. Results: The tablets had the following characteristics: weight, 659.25 ± 7.96 to 661.65 ± 6.53 mg; hardness, 7.05 ± 0.21 to 9.60 ± 0.40 kgf; friability, 0.212 to 0.292 %; and drug content, 91.47 ± 0.53 to 112.50 ± 4.14 %. In batches prepared with ethyl cellulose, Eudragit L-100, and hydroxypropyl methylcellulose, drug release increased with a decrease in pH. However, matrix tablets prepared with hydroxyethyl cellulose displayed the highest drug release at pH 4.0 with Cmax of 108.75 % and T50% of 30.86 min; thereafter, drug release decreased with increase in pH. The pattern of drug release was Hec &gt; Hpc &gt; Eud &gt; Etc in most media with more drug release in acidic than at alkaline pH. Conclusion: Release of ciprofloxacin from the formulated matrix tablets was pH-sensitive in vitro. This should be taken into consideration in designing sustained release oral form of ciprofloxacin.

Formulation and Evaluation of Sustained Release Linezolid Tablet using Natural Antibacterial Polymer - &lt;i&gt;Aegle marmelos&lt;/i&gt;

The objective of the current research study was to formulate and evaluate a sustained-release linezolid tablet using the natural antibacterial polymer Aegle marmelos. The natural gum of Aegle marmelos is becoming increasingly used in pharmaceutical formulations as a beneficial medication with excipients. Natural-based plant materials are biocompatible, free of side effects, biodegradable, and economic. Therefore, in order to maintain the drug releases from the matrix system, Aegle marmelos fruit gum as a natural polymer and HPMC grade (K100M) as a synthetic polymer were used in the formulation of the linezolid matrix tablet. The formulation of sustained-release matrix tablets included the wet granulation technique. The formulated matrix tablets were evaluated in terms of weight variation, hardness, diameter, physical appearance, friability, thickness, and in vitro drug release. Each formulation’s matrix tablet passed the required physical assessment tests. The formulation analyses of the tablets’ dissolution showed sustained releases of drugs for up to 10–12 hours. Additionally, several polymer combinations and fillers were used to improve drug release factors using the 32 factorial design approach, drug release kinetics were optimized, and the antibacterial study was evaluated.

Development of Delayed-Release Matrix Tablets Comprising Solid Dispersion of Mefenamic Acid

Mefenamic acid (MA), a member of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), has been widely use to relief pain and inflammation. Its medical uses are limited by poor aqueous solubility resulting in low bioavailability and gastric irritation. The aim of this study was to develop a mefenamic acid delayed-release matrix tablet formulation using solid dispersion (SD). Delayed-release drug delivery systems were designed to retard drug release in upper gastrointestinal tract avoiding gastrointestinal (GI) adverse reactions. SDs of MA were successfully prepared by solvent evaporation method employing methanol as a solvent. SDs incorporated surfactant and super disintegrant gave much higher rates of dissolution than SDs with combined carriers (PEG and surfactant), SD containing PEG and pure drug, respectively. The optimal SD containing MA:PEG4000:poloxamer188:crospovidone in the ratio 1:8:1:3 exhibited higher amount of drug release up to 8-fold compared with pure MA. FTIR and DSC were performed to identify the physicochemical interaction between drug and polymers. The resulting data justified that no change in the chemical structure of MA and the crystalline MA transformed into the amorphous state after preparation. The formulation F4 delayed-release tablet comprising SD of MA dissolved less than 4 % in artificial gastric fluid in the initial 2 h and released more than 95 % at 3 h in the artificial intestinal fluid. Accordingly, formulation F4 containing polyethylene oxide as a time-controlled matrix-forming polymer was a promising delayed-release solid dispersion system of MA. HIGHLIGHTS The present study demonstrated a mefenamic acid delayed-release matrix tablet formulation using solid dispersion (SD) The optimal SD of mefenamic acid exhibited higher amount of drug release (8-fold) compared with that of the pure drug The tablet formulation F4 containing polyethylene oxide is capable of releasing mefenamic acid in a typical delayed-release profile GRAPHICAL ABSTRACT

Formulation design and optimization of sustained release tablet dosage form of Diacerein

Diacerein is both an anti-inflammatory drug and an anti-arthritic agent. At present, no sustained release dosage form of Diacerein is commercially available. The aim of the study was to develop an optimized formulation of sustained release tablet dosage form of Diacerein that will be highly patient compliant. A three-level full factorial design was employed to develop nine different formulations of matrix tablets using a combination of Methocel K100M CR and Methocel K4M CR polymer at different ratios. The physical evaluation of both the drug-excipient powder mixtures and tablets of the nine formulations were performed and results were found to be within acceptable ranges for all tests. Dissolution profiles of tablets were obtained and the kinetics of drug release from the matrix tablets were determined by employing various mathematical models. The release data were simulated in Design Expert Software to carry out statistical analysis and the effect of both polymers on release patterns were observed after 1, 4 and 8 h in terms of contour plots and 3D surface plots, which were found to be statistically significant (p < 0.05). Finally, the overlay plot was obtained from which the optimized formulation of Diacerein was determined.

Personalised 3D-Printed Mucoadhesive Gastroretentive Hydrophilic Matrices for Managing Overactive Bladder (OAB).

Overactive bladder (OAB) is a symptomatic complex condition characterised by frequent urinary urgency, nocturia, and urinary incontinence with or without urgency. Gabapentin is an effective treatment for OAB, but its narrow absorption window is a concern, as it is preferentially absorbed from the upper small intestine, resulting in poor bioavailability. We aimed to develop an extended release, intragastric floating system to overcome this drawback. For this purpose, plasticiser-free filaments of PEO (polyethylene oxide) and the drug (gabapentin) were developed using hot melt extrusion. The filaments were extruded successfully with 98% drug loading, possessed good mechanical properties, and successfully produced printed tablets using fused deposition modelling (FDM). Tablets were printed with varying shell numbers and infill density to investigate their floating capacity. Among the seven matrix tablet formulations, F2 (2 shells, 0% infill) showed the highest floating time, i.e., more than 10 h. The drug release rates fell as the infill density and shell number increased. However, F2 was the best performing formulation in terms of floating and release and was chosen for in vivo (pharmacokinetic) studies. The pharmacokinetic findings exhibit improved gabapentin absorption compared to the control (oral solution). Overall, it can be concluded that 3D printing technology is an easy-to-use approach which demonstrated its benefits in developing medicines based on a mucoadhesive gastroretentive strategy, improving the absorption of gabapentin with potential for the improved management of OAB.

Formulation and Characterization of Sustained Release Matrix Tablet of Pantoprazole

Pantoprazole is a proton pump inhibitor prodrug used in the treatment of gastric, duodenal ulcers and gastro esophageal reflux disease (GERD), Zollinger- Ellison syndrome. This is the most popular drug used in cure and maintenance therapy of peptic ulcer along with antibiotics. It suppresses the acid production by inhibiting the H+ K+ ATPase. Pantoprazole must be absorbed in the gastrointestinal tract and because it is unstable under acidic conditions, enteric delivery systems are required. The purpose of this study was to prepare matrix tablet using eudragit Rs 100, eudragit S100, and HPMC. On the basis of above result the formulation showed satisfactory result as it has the maximum release i.e. F5 66.50%in 10 hrs. Result of our study suggest that the matrix tablet containing pantoprazole may be suitable for the anti ulcer drug.

INFLUENCE OF PARTIALLY AND FULLY PREGELATINIZED STARCH ON THE PHYSICAL AND SUSTAINED-RELEASE PROPERTIES OF HPMC-BASED KETOPROFEN ORAL MATRICES

Objective: This study aims to investigate the effect of two types of pregelatinized starch on the physical performance of HPMC matrices containing Ketoprofen as a model drug. Methods: The design of the experiment was inspired by the monothetic analysis, in which testing factors or causes is done one factor or cause at a time, to achieve system improvements. Tablets were prepared by direct compression. The impact of the type of modified starch on the tablet's physicochemical properties was studied by testing for weight variation, friability, hardness, and drug release properties. PCP dissolution software was used to investigate the kinetics of drug release from matrix tablet formulation. Results: The impact of the type of modified starch on tablet physicochemical attributes revealed that the weight variation of tablets was affected by the amount of modified starch used and that the combination of 64.7% partially pregelatinized starch (StarchÒ 1500) with 9.5% HPMC (F8) was found to be the better in terms of weight variation (%RSD= 1.73%) when compared with those containing fully pregelatinized starch (LYCATABÒ). All formulation runs have friability that complies with pharmacopeial limits of less than 1% loss upon test conduction except for (F1). Formulations containing LYCATABÒ showed better friability than those containing StarchÒ 1500, and similar results were observed in tablet hardness as well, in which the formulation containing the highest LYCATABÒconcentration showed a significant increase in mechanical strength (P = 0.0004) than those containing the highest concentration of StarchÒ 1500. Finally, all formulations containing LYCATABÒexhibited sustained-release behavior, less than 60% of the drug was released from matrices over 14 h, and it is believed that the drug is transported via Fickian diffusion and followed either Higuchi or Peppas model (n&gt;0.5), while all formulations containing StarchÒ 1500 released ~90% of the drug around 2 h, this might probably be due to the high disintegration effect of the partially pregelatinized starch, which is lost upon full pregelatinization. Conclusion: Tablet weight variation, hardness, friability, and T50% were found to be influenced by both the type and concentration of modified starch used. While drug release characteristics were greatly affected by the type of modified starch used. For sustain-release formulations, only fully pregelatinized starch is thought to be suitable.

Formulation and Evaluation of Sustained Release Matrix Tablet of Nimesulide Using Pomegranate Peel and Acacia

The main objective of the study is the formulation and evaluation of sustained release matrix tablet of Nimesulide using pomegranate peel and acacia as natural polymer. The preformulation study of Nimesulide was conducted and λmax was found at 300 nm. The sustained release matrix tablet was prepared using Pomegranate peel as Release rate retardant, Acacia as polymer, Polyvinylpyrrolidone K30 as Binder, Isopropyl alcohol as Granulation solution, Micro Crystalline Cellulose as Diluent, Magnesium stearate as Lubricant and Talc as Glidant. Several formulations were prepared by taking different drug concentration in Pomegranate peel (Release rate retardant) with varying ratio of binder to lubricants. Various formulations of sustained release matrix tablet of Nimesulide F1, F2, F3, F4, F5, F6 was prepared. The prepared granules were evaluated for different parameters like Bulk density, Tapped density, Angle of repose, Carr’s index, Hausner’s ratio which shows the excellent flow properties of formulation. The physical characteristic of Nimesulide sustained release matrix tablets (F1 to F6) such as thickness, diameter, hardness, friability, weight variation and drug content were determined and results of the formulations (F1 to F6) found to be within the limits specified in official books. The drug content of all the formulation were found to be in the range of 99.59 to 99.83 % w/w, which is within the specified limit as per Indian Pharmacopoeia 1996 (i.e. 90-110% w/w). The drug released from formulation F1 to F3 was found to be 93.7, 92.9 and 92.2 % for Nimesulide respectively. The drug released from formulation F4 to F6 was found to be 94.1, 93.9 and 92.8% for Nimesulide respectively. The release rate of F1 and F4 was found to be higher when compared to other formulations this is due to increase in the concentration of polymer. These results are indicating that has higher drug retarding ability for long duration. All the formulations were analyzed for stability testing. All the formulations from F1 to F6 were found to be stable.

Formulation and evaluation of theophylline sustained release matrix tablets using synthetic polymers

The aim of present work was to develop theophylline sustained release tablets which could improve patient compliance towards the effective management of asthma The polymers, HPMC (Hydroxy propyl methyl cellulose) K4M, HPMC K100M, Eudragit, Chitosan in blending and granulation stage of processing and evaluate their physico-chemical properties. The precompression limits of the powder blends used for the preparation of sustained-release tablets were in an acceptable range of pharmacopeial specification with excellent flow and good compressibility. Wet granulation method prepared tablets using different grades of polymers HPMC K100, HPMC K4M, Eudragit, Chitosan. The active ingredient, release retardants, diluents, fraction of polymer are mixed to make wet mass for granulation. The in- vitro release was prolonged to 12 hours using HPMC K4M, HPMC K100M, Chitosan, Eudragit. F9 formulation prolonged the theophylline release in 12 hours. The effect of polymer on drug release was studied. Thus, sustained release matrix tablets can promise better patient compliance through reduction in over-all dose and dosage regimen, which can be of excessive support to treat chronic disease.