Compressibility Characteristics of Matrices Prepared with Ethylcellulose Aqueous Dispersion

Granules of acetaminophen (APAP) and Lactose Fast Flo were prepared by wet granulation method using Surelease aqueous dispersion as a granulating liquid. Acetaminophen granules containing different total solids (from Surelease) were compacted into tablets using instrumented tablet press to investigate the effect of the levels of Surelease (total solids) on the compressional properties of various formulations. Measurements were made of their compressibility, force displacement, works and forces analysis during compaction. All formulations containing Surelease utilized the compaction energy better than formulations of the same composition prepared without Surelease. As the level of total solids from Surelease was increased in the formula, the compressibility characteristic was enhanced. Granules with Surelease exhibited better deformation and densification behaviors and gave tablets of better mechanical strength compared to control tablets.     

Mechanisms of Drug Release from Matrices Prepared with Aqueous Dispersion of Ethylcellulose

The objective of this study was to investigate the mechanism of acetaminophen (APAP) release from tablets prepared by the wet granulation method using an aqueous polymeric dispersion (Surelease) as a granulating agent. Tablets compressed from granules containing 10% w/w acetaminophen and 13.44% w/w total solids from Surelease released only 52.4% w/w drug after 120 min of dissolution testing, while controlled tablets without Surelease released 94.1% w/w drug. In order to prepare control tablets of 6.8 Kp hardness value, the upper compressional force recorded was 15.87 kN while tablets containing 13.44% w/w of total solids from Surelease had a recorded force of 6.28 kN. The drug release from tablets prepared with Surelease as a granulating liquid followed the diffusion-controlled model for an inert porous matrix     

Effect of Eudragit Resins and Dibasic Calcium Phosphate on the Compation and Dissolution Behavior of Directly Compressible Controlled-Relase Theophylline Tablet

Abstract

The compaction behavior and release property of tablets made by the combined formulations of Eudragit RLPM and RSPM with or without diabasic calcium phosphate anhydrous (DCPA) using direct compaction were examined. The larger the amount of Eudragit RSPM or DCPA the higher the value of the tensile strenght. A linear realationship was found in the lorgrithm of tensile strength plotted against the porosity of the compacts. The Heckel plot was also used ot evalute the compaction behaviour of tablets. The results indicate that Eudargit RSPM and DCPA are responsible for the good compressiblity of compacts. The contact angle of tablets without DCPA became samller with an increase in the Eudragit RSPM, but exhibited a higher contact angle than tablests with DCPA. The controlled release behavior of theophylline from tablets without DCPA was found and showed a pH-independent property, whereas tablets with DCPA were pH-dependent and exhibited a faster dissolution than tablests without DCPA. The result suggests that controlled-relase and better compressible tablets can be prepared by adjusting the combinatin ratios of Eudragit RLPM and RSPM with or without DCPA by direct compression.     

Influence of punch geometry (head-flat diameter) and tooling type (‘B’ or ‘D’) on the physical–mechanical properties of formulation tablets

The presented study assessed the influence of punch geometry (head-flat [HF] diameter) and tooling type (‘B’ or ‘D’) on the physical–mechanical properties of tablets prepared by direct-compression of two guaifenesin (25% or 40% w/w) formulations. Tablets of both formulations were prepared on instrumented, single-layer, rotary tablet press using 10?mm, flat-faced, ‘B’ or ‘D’-type tooling with different HF diameters, and compression forces (CF) ranging from 5 to 25?kN with 5?kN increments. The tablets were evaluated for dimensions, weight variation, tensile strength (TS), friability, and capping index. In general, tablets prepared using ‘D’ tooling showed a significantly (p?<?0.05) higher TS compared to those prepared using ‘B’ tooling, likely due to higher dwell-times associated with ‘D’ tooling. Formulations containing 25% w/w guaifenesin showed a significantly (p?<?0.05) higher TS compared to those containing 40% w/w guaifenesin, at given compression CF, punch geometry, or tooling type. This could be due to the higher ratio of Prosolv^® SMCC contributing to the compressibility. For both formulations compressed using ‘B’ tooling, differences in TS profiles were observed between different HF tooling. The TS of these tablets increased significantly with increasing HF diameter. For formulations compressed using ‘D’ tooling, this trend was observed only up to a CF of 15?kN, beyond which the TS plateaued, possibly due to work-hardening of the formulation at higher CF. These formulations also exhibited capping at CF above 15?kN and with higher HF diameters. The study showed a significant influence of punch geometry and tooling type on the physical properties of tablets.     

Formulation and Compaction of Microspheres

Abstract

The factors affecting the tabletability of formulations containing uncoated and/or coated microspheres were discussed by presenting a case study. The size and shape, as well as surface properties of microspherical particles, the type and amount of coating agent, selection of the external additives, and the rate and magnitude of the pressure applied were found to be the most critical factors to be considered in order to obtain and maintain the desired drug release properties of the microspheres. It was found that microcrystalline cellulose was needed in order to produce satisfactory beads in terms of size, shape and surface characteristics. The microsphere formulations, which were found to be highly sensitive to lubrication, were more compressible than their powder forms, but produced much weaker tablets. When coated with Surelease, increasing the amount of coating on the pellets reduced the tensile strength of their compacts. Compaction of the microspheres at high velocities resulted in a decrease in the tensile strength values and an increase in the volumetric strain recovery values. Dissoultion studies revealed that, regardless of the amount of coating applied, the coated microspheres lost their sustained release properties during compaction.     

Investigation of Ethylcellulose as a Matrix Former and a New Method to Regard and Evaluate the Compaction Data

Abstract

Three types of ethylcellulose—having different molecular weights, i.e., different viscosity grades (7, 22, 50 cP)-were used for our polymer compression tests for the production of matrix tablets. The production methods used were direct compression and wet granulation. We tested the compactability, the compressibility, and the energy involved in compaction by the use of F-D curves and the controlled drug release from the ethylcellulose matrix tablets using the above-mentioned methods. A lower viscosity grade in ethylcellulose is more compressible than the higher grade. Wet-granulated ethylcellulose also shows a better compactibility than directly compressed ethylcellulose. Our investigation indicates also that the dissolution rates are indirectly proportional to the hardness of the tablets. Furthermore, wet-granulated tablets produce a more rapid drug release than those which are directly compressed.     

Polyols as filler-binders for disintegrating tablets prepared by direct compaction

Background: Although polyols are frequently used as tablet excipients in lozenges, chewing tablets, and orodisperse tablets, special directly compressible (DC) forms are recommended as filler-binder in common disintegrating tablets. Aim: In this article, DC types of isomalt, lactitol, mannitol, sorbitol and xylitol are evaluated. Method: Tablets of both lubricated and unlubricated DC polyols and theophylline tablets were compressed at different forces using a compaction simulator or a motorized hydraulic press. Disintegration times (without disks) and dissolution rate were measured according to Ph.Eur. Results: Compaction profiles show that the DC forms of isomalt, mannitol and sorbitol have sufficient compactibility and a low lubricant sensitivity. The crushing strengths of tablets, prepared from DC lactitol and xylitol, are too low for practical use. Because of their reduced hygroscopicity and smaller capping tendency as compared with DC sorbitol, DC types of isomalt and mannitol seem to be the most convenient filler-binders. Because of their high water solubility, tablets prepared from polyols erode rather than disintegrate. Tablet formulations with theophylline as a test drug and DC isomalt or DC mannitol as filler-binder show that both products have their own limitations: DC mannitol gives more adhesion problems than DC isomalt. On the other hand, the disintegration time and drug dissolution rate for tablets containing DC mannitol is faster than for tablets containing DC isomalt. Conclusions: Of the DC polyols investigated, both DC isomalt and DC mannitol are the most suitable filler-binders for disintegrating tablets, prepared by direct compaction.     

Controlled-Release Matrix of Acetaminophen-Ethylcellulose Solid Dispersion

Abstract

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Lactose fast-flo as diluent and 1% magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model.     

Comparison of two Varieties of Microcrystalline Cellulose as Filler-Binders II. Hydrochlorothiazide Tablets

Abstract

In tests of direct-compression hydrochlorothiazide tablets prepared with either of two varieties of microcrystalline cellulose (Avicel PH 101 and Avicel PH 102), PH 102 tablets had better mechanical properties (owing to lower compressibility of mixtures and greater Interparticle bonding), while PH 101 tablets released the active principle faster. These differences are related to observed differences In tablet micropore structure.     

Eudragit® RS PO/RL PO as rate-controlling matrix-formers via roller compaction: Influence of formulation and process variables on functional attributes of granules and tablets

The influence of plasticizer level, roll pressure and sintering temperature was investigated on the granule properties, tablet breaking force and theophylline release from tablets. Nine formulations using theophylline as a model drug, Eudragit^® RL PO, Eudragit^® RS PO, or both as a matrix former and triethyl citrate (TEC) as a plasticizer were prepared. The formulations were roller compacted and the granules obtained were evaluated for particle size distribution and flowability. These granules were compacted into tablets at a compression force of 7?kN. The tablets were thermally treated at different temperatures (50 and 75°C) for 5?h and were evaluated for breaking force and dissolution. Increase in roll pressure and TEC levels resulted in a progressive increase in the mean particle size of the granules. The flowability of the granules also improved with increasing roll pressures and TEC levels. Tablet breaking force increased with an increase in TEC levels and sintering temperatures. But these effects were significant only at the highest level of plasticizer and sintering temperature respectively. For the tablets containing Eudragit^® RS PO, theophylline release decreased proportionately with increase in TEC levels and sintering temperatures. Tablets containing either Eudragit^® RL PO or a mixture of RS PO and RL PO failed to impart an extended-release property to the tablets at the studied variables i.e. roll pressure, TEC levels and sintering temperature. It was clearly demonstrated that with suitable optimization of these parameters, the release-rate of a water soluble drug from the matrix tablets prepared via roller compaction can be finely controlled.     

The effect of ultrasonic vibration on the compaction characteristics of ibuprofen

An ultrasonic (US) compaction rig has been developed, capable of providing compaction pressure together with high-power ultrasonic vibrations of 20 kHz to a powder or granular material in a die. The rig has been used to investigate the effect of ultrasound on the compaction properties of ibuprofen, a drug with poor compaction properties which produces tablets that are weak and frequently exhibit capping. It was found that coherent ibuprofen tablets could be prepared by ultrasound-assisted compaction at pressures as low as 20-30 MPa. Application of ultrasound before and after compaction was found not to be as effective as ultrasound applied during compaction. The breaking forces of the tablets produced with ultrasound applied during compaction were found to be consistently significantly higher than when compaction was performed conventionally, or with ultrasound applied before or after compaction. Application of ultrasound during compaction made it possible to increase tablet mechanical strength, typically by a factor of 2-5. It was concluded that pressure should be applied together with ultrasound in order to achieve a better acoustical contact, which is required to transmit vibrations from the horn to the material, and also to bond the surfaces of the particles.

Ultrasound application during ibuprofen compaction also resulted in an increase in the apparent density, in relation to the apparent density of conventionally prepared tablets, of up to 14.4%. Ultrasound appears to improve particle rearrangement and provides energy for partial melting of particle asperities and subsequent fusion of particle surfaces, so as to increase interparticulate bonding. Solid bridge formation was thought to result in a reduction of void space, which in turn reduced the rate of water penetration into the compacts and consequently increased disintegration and dissolution times.

It was found that the results of ultrasound-assisted compaction are influenced by formulation and US time. When ibuprofen was mixed with a second material, such as dibasic calcium phosphate dihydrate (DCP) or microcrystalline cellulose (MCC), stronger tablets were prepared by ultrasound-assisted compaction compared to the compacts containing no filler. Positive interactions were considered to have occurred due to ultrasound-induced bonding between the two materials. With an increase in DCP and MCC concentration in ibuprofen formulations, disintegration and drug dissolution rates of the tablets produced with ultrasound significantly increased.

Using temperature-sensitive labels it was found that thermal changes occurred in powdered solids undergoing ultrasound-assisted compaction. Increases in the temperature of tablets were related to US amplitude and US time. With an increase in US amplitude from 5 to 13 µm, the temperature of the DCP tablet surface increased from 40 to 99°C. With an increase in US time from 1 to 5 sec, the temperature of the surface of ibuprofen tablets increased from 43 to 60°C. Increased tablet temperature was thought to be due to ultrasonic energy dissipation turned into heat.

X-ray powder diffraction (XRD) studies of ibuprofen tablets prepared by ultrasound-assisted compaction at 32 MPa revealed that no changes in chemical or/and crystalline structure of the material occurred when ultrasound was applied for up to 5 sec (US amplitude 7 µm). An XRD study of DCP tablets produced by ultrasound-assisted compaction at 32 MPa with ultrasound of different amplitudes (5, 7, 13 µm) applied for 2 sec indicated that no material deterioration occurred in all the tested samples.     

Formulation and Release Kinetics of Sustained Release Phenylpropanolamine Hydrochloride Granules and Tablets

Abstract

Sustained release phenylpropanolamine hydrochloride (PPH) granules and tablets were prepared using HPMC, HPMC and SCMC, Eudragit RS, Eudragit RS+L or HPMC + Eudragit RS matrices. The release pattern of PPH from the prepared granules and tablets was found to be in the following order HPMC > HPMC + SCMC > RS > RS + 1> HPMC + RS. The results revealed that, although the drug concentration was kept constant in all the prepared granules and tablets, the drug release from these formulations was clearly different and depends mainly on the type of matrix used. The presence of Eudragit L with Eudragit RS and Eudragit RS with HPMC resulted in a marked decrease in the drug release compared with that obtained from the matrix containing HPMC or Eudragit RS alone. The release data of PPH from the prepared granules and tablets were treated mathematically according to zero order, first order, Langenbuchar, modified Langenbucher and Higuchi models. The results revealed that no one model was able adequately to describe the drug release profiles from these formulations. In-vivo studies in human volunteers showed that, the peak urinary excretion of PPH occurred over a sustained period from 2 to 6.5 hr in case of HPMC + SCMC tablets and from 2 to 10 hr in case of either RS+L or HPMC + RS tablets.     

Effects of Lubricant Level,Method of Mixing,and Duration of Mixing on a Controlled-Release Matrix Tablet Containing Hydroxypropyl Methylcellulose

Abstract

The effects of the lubricant magnesium stearate at different concentrations, mixing shear rates, and mixing times on the tablet properties and drug dissolution from controlled-release matrix tablets containing hydroxypropyl methylcellulose 2208, USP (METHOCEL® K4M Premium) have been studied. Diphenhydramine HCl and hydrochlorothiazide were chosen as the model drugs. Spray-dried hydrous lactose (Fast Flo Lactose-316®) and anhydrous dibasic calcium phosphate (A-TAB®) were chosen as the model excipient/fillers. The impact of magnesium stearate on the mechanical strength of tablets appeared to be dependent on the bonding mechanism of the components of the powder mix. Tablets containing A-TAB, which compacts via a brittle fracture mechanism, were harder and had significantly better friability patterns than those prepared using Fast Flo Lactose-316. The compaction of Fast Flo Lactose-316 appears to be a combination of brittle fracture and plastic deformation. Mixes containing lower levels of lubricant (0.2%) generated tablets that had higher crushing strengths than those with higher lubricant levels (2.0%). Drug release was impacted to the greatest extent by the solubility of the drug and excipient/filler but was only slightly affected by the level of magnesium stearate and duration of mixing.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

Abstract

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

Optimization of piribedil mucoadhesive tablets for efficient therapy of Parkinson’s disease: physical characterization and ex vivo drug permeation through buccal mucosa

Objective: The aim of this study was optimization of buccal piribedil (PR) mucoadhesive tablets to improve its low bioavailability and provide controlled release for the treatment of Parkinson’s disease.

Methods: Buccal tablets were prepared by direct compression method using carbomer (CP), carboxymethyl cellulose (CMC), and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Physical properties of powder mixtures and buccal tablets were evaluated. Physicochemical compatibility between ingredients was investigated with infrared spectroscopy and differential scanning calorimetry analysis. In vitro dissolution profiles and drug release kinetics of buccal tablets were investigated. Mucoadhesion and ex vivo permeation studies were performed using sheep buccal mucosa.

Results: Powder mixtures demonstrated sufficient flow properties and physical characteristics of all tablet formulations were within compendia limits. Tablet ingredients were absent of any chemical interactions. CP tablets displayed slower drug release compared to HPMC tablets with zero order release, while CMC tablets lost their integrity and released entire drug after 6?h following Higuchi model. All formulations displayed adequate mucoadhesion and steady state flux of PR through buccal mucosa were higher with HPMC compared to CP-containing tablets.

Conclusion: Overall, HPMC was found to combine desired controlled release and mucoadhesion characteristics with sufficient pharmaceutical quality for optimization of buccal tablets. Piribedil mucoadhesive buccal tablets designed for the first time may introduce a new alternative for the treatment of Parkinson’s disease.     

Effect of some commercial grades of microcrystalline cellulose on flowability, compressibility, and dissolution profile of piroxicam liquisolid compacts

The technique of liquisolid compacts is a promising method toward enhancing the dissolution of poorly soluble drugs. Lower flowability and compressibility is one of the limitations of this technique. The evaluation of effects of different grades of microcrystalline cellulose (MCC) on flowability, compressibility, and dissolution of liquisolid systems were the aims of this study. For this means, several formulations were prepared using various grades of MCC as carrier. Propylene glycol (PG), silica, and sodium starch glycolate were used as nonvolatile solvent, coating material, and disintegrant, respectively. Then flowability, friability hardness, and dissolution rate of prepared formulations were studied. The effect of tablet aging on mentioned properties was also investigated. The results showed that among the evaluated different grades of MCC, compacts containing MCC PH 101 and 102 showed better dissolution profiles. Harder compacts were obtained using MCC PH 101 and 200 as carriers. Better flowability was observed in compacts containing MCC PH 101. Also, these compacts demonstrated acceptable friability. Aging had no effect on hardness and dissolution profile of liquisolid tablets. It could be concluded that MCC PH 101 is a suitable carrier for preparing liquisolid systems for having acceptable flowability, friability, hardness, and dissolution profile.     

Comparison of Disintegrant and Binder Activity of Three Corn Starch Products

Abstract

This study demonstrates the differences obtained when using different corn starch products as both binder and disintegrant in pharmaceutical tablets. Formulations made with Fluftex W, Tablet White and Purity 21 starches were compared. In addition, Avicel PH101 was used in this study as a benchmark component whose properties are well understood.

Four test formulations containing hydrochlorothiazide were prepared by wet granulation. Starch was incorporated in both powder and paste form. All granulations were found to possess similar traits when evaluated based upon geometric mean diameter, particle size distribution, bulk/tap densities, powder flow rate and surface characteristics.

Tablets prepared from these granulations were shown to be similar when evaluated for degree of friability, weight and content uniformity. All starch formulations disintegrated within 30 seconds and produced similar dissolution profiles. Tablets produced with Avicel, however, were found to exhibit significantly longer disintegration times than the starch formulations. In addition, these tablets displayed a dissolution profile that was significantly different than the starch formulations, particularly during the earlier stages of the dissolution process.

When monitoring compression and ejection forces required to produce tablets of the same degree of hardness (≈6kg), Fluftex W and Tablet White granulations were found to use significantly lower forces than the Purity 21 granulation. This may be indicative of Fluftex W and Tablet White's superiority over Purity 21 in terms of binder capacity.     

Controlled-Release Theophylline Tablet Formulations Containing Acrylic Resins,II. Combination Resin Formulations

Abstract

Theophylline tablet formulations containing a combination of cationic and anionic acrylic resins were prepared and evaluated. Equal amounts of Eudragit RSPM (cationic resin) and Eudragit L100 (anionic resin) were included at the 15% level (total polymer content) into the tablet formulations. Pressure-hardness profiles with theophylline-resin compacts (4:1) demonstrated that compacts containing the RSPM resin were the most compressible. The dissolution profiles for theophylline in acidic media showed slower release rates from tablets containing the combined resins than from those containing each of the single resins. It was proposed that this decrease in drug release rate was a result of a solid state interaction between the oppositely charged polymers. As the amount of retardant in the matrix increased, the release rates in acidic media decreased. In pH 7.4 phosphate buffer, much faster release was seen due to the higher solubility of the Eudragit L-100 resin at this pH level. Tablet hardness between the range of 6.8 kg to 15 kg showed minimal influences on the dissolution rate. Recompression and relubrication of the tablet formulation containing both polymers, produced a decrease in release rates of theophylline from the tablet matrix.     

Comparison of Disintegrant and Binder Activity of Three Corn Starch Products

Abstract

This study demonstrates the differences obtained when using different corn starch products as both binder and disintegrant in pharmaceutical tablets. Formulations made with Fluftex W, Tablet White and Purity 21 starches were compared. In addition, Avicel PH101 was used in this study as a benchmark component whose properties are well understood.

Four test formulations containing hydrochlorothiazide were prepared by wet granulation. Starch was incorporated in both powder and paste form. All granulations were found to possess similar traits when evaluated based upon geometric mean diameter, particle size distribution, bulk/tap densities, powder flow rate and surface characteristics.

Tablets prepared from these granulations were shown to be similar when evaluated for degree of friability, weight and content uniformity. All starch formulations disintegrated within 30 seconds and produced similar dissolution profiles. Tablets produced with Avicel, however, were found to exhibit significantly longer disintegration times than the starch formulations. In addition, these tablets displayed a dissolution profile than was significantly different than the starch formulations, particularly during the earlier stages of the dissolution process.

When monitoring compression and ejection forces required to produce tablets of the same degree of hardness (≈6kg), Fluftex W and Tablet White granulations were found to use significantly lower forces than the Purity 21 granulation. This may be indicative of Fluftex W and Tablet White's superiority over Purity 21 in terms of binder capacity.     

Effect of Aging on the Bioavailability of Nitrdfurantoin Tablets Containing Carbopol 934

Abstract

This article reports a study of two nitrofurantoin tablet formulations differing in the percentage of Carbopol 934 used as binder. The tablets of both formulations each contained 50 mg of nitrofurantoin. Those of formulation A contained 0.625 mg of Carbopol 934, and those of formulation B 1.25 mg. When freshly prepared, tablets of both formulations were bioequivalent to capsules containing 50 mg of nitrofurantoin, but a year's storage at 40°C and 60% relative humidity caused a significant decrease in the bioavailability of nitrofurantoin from formulation B, whereas formulation A was still bioequivalent to capsules. USP XXI Ed. Method II successfully reflected the observed variations in bioavailability, but not Method I.