Influence of plasticizer type and coat level on Surelease film properties

Two commercially available formulations of aqueous ethylcellulose dispersion differing in their plasticizer, i.e., Surelease/E-7-7050 containing dibutyl sebacate (DBS) and Surelease/E-7-7060 containing glyceryl tricaprylate/caprate (GTC), were evaluated and compared for their film properties as a function of polymeric coat level. Ibuprofen tablets were coated at 1, 2, 3, and 5% w/w levels using each Surelease formulation, and the coated tablets were evaluated for their drug release characteristics, coat reflectivity (gloss), surface texture, Brinell hardness, and elastic modulus. The drug release was dependent on the coat level and followed Hixson-Crowell cube-root model at 1% coat level. However, at > or = 2% coat levels, the release from tablets coated with GTC plasticized formulation appeared to be best described by non-Fickian release mechanism and that from tablets coated with DBS plasticized formulation appeared to follow apparent zero-order release mechanism. At equal coat levels, tablets coated with GTC plasticized Surelease yielded lower drug release rates, higher reflectivity (gloss), lower surface roughness, higher Brinell hardness, and lower elastic modulus than those coated with DBS plasticized formulation. A good correlation was observed between the drug release rates and the reflectivity and surface texture of the coated tablets. The film-coats of GTC plasticized formulation were harder and more elastic than those of DBS plasticized formulation indicating better mechanical integrity.     

Tensile Properties of Free Films Cast from Aqueous Ethylcellulose Dispersions

Free films of two commercially available formulations of aqueous ethylcellulose dispersion differing only in plasticizer content (Surelease/E-7-7050 without silica and E-7-7060 containing dibutyl sebacate and glyceryl tricaprylate/caprate as plasticizers, respectively) were cast and coalesced at temperatures ranging between 30 and 70°C. Mechanical properties of these films were measured using tensile stress analysis. Three mechanical parameters, namely, tensile strength, work of failure, and elastic modulus, were computed from the load-time profiles of these films. The results showed that the tensile strength and elastic modulus values of the films cast from both formulations increased with the corresponding increase in coalescence temperature up to 60°C, beyond which no significant differences were observed. In the case of work of failure, however, the difference between the two formulations was observed above 60°C. The films cast from Surelease/E-7-7050 formulation without silica (dibutyl sebacate as the plasticizer) were relatively softer than those from Surelease/E-7-7060 formulation (glyceryl tricaprylate/caprate as the plasticizer). At coalescence temperatures above 50°C, the films cast from both formulations exhibited temperature-dependent plastic deformation.     

Aqueous Ethylcellulose Dispersion of Ethylcellulose. I. Evaluation of Coating Process Variables

Formulation and process variables play an important role in the film-forming properties of coating polymers. Three selected independent coating process variables, namely, percent solids content in the coating polymeric dispersion, inlet-air temperature, and spray rate of the polymeric dispersion, were investigated in this study to determine their effect on the performance characteristics of tablets coated with a plasticized aqueous ethylcellulose dispersion (Surelease) in a fluid-bed equipment. Response surface methodology (RSM) was utilized to study the complex relationship between these process variables and selected response variables. Three response variables were considered, namely, rate of drug release from the untreated coated tablets and the thermal-treated coated tablets and microindentation hardness of the untreated coated tablets. A 12-point factorial experimental design was utilized, and three-dimensional (3-D) response surface plots were generated using a second-order polynomial model. The model provided information needed to predict optimal process conditions. Drug release from the coated tablets followed zero-order kinetics. Inlet-air temperature was found to be the most critical process variable for all the three response variables studied. A correlation was observed between the drug release rate and the microindentation hardness of the applied polymeric coat in the case of untreated coated tablets. The 3-D response surface plots indicated that lower rates of drug release from the coated tablets may be obtained by using high inlet-air temperature and low spray rate of the polymeric dispersion during coating.     

Influence of type and level of water-soluble additives on drug release and surface and mechanical properties of Surelease films

Ethylcellulose in combination with water-soluble additives has been used in the development of microporous membrane-coated dosage forms. In the present study, application of three types of water-soluble additives, namely polyethylene glycols (PEG 400, 3350, and 8000), maltodextrins (Maltrin M150, M100, and M040 in the order of lower to higher average polymer size and molecular weight; dextrose equivalence 16.9, 11.1, and 4.8, respectively), and xylitol, as porosity modifiers in the films of a commercially available aqueous ethylcellulose dispersion (Surelease/E-7-7060 plasticized with glyceryl tricaprylate/caprate) was investigated. The effect of type and level of these additives on drug release characteristics and surface and mechanical properties of the polymeric films was studied. Each additive was incorporated at 20 and 30% levels in the polymeric dispersion based on its solids content. Ibuprofen tablets were coated using the polymeric dispersion with and without additive at 3% w/w coat level in a fluid-bed equipment. The coated tablets were evaluated for their drug release rate, coat reflectivity (gloss), Brinell hardness, and elastic modulus. Differential scanning calorimetric analysis of the films was performed to determine the physico-chemical changes in the applied film-coats. The rate of drug release, hence film porosity, was observed to be dependent on the type and level of the additive added. The molecular weight of the additive and its concentration in the polymeric dispersion had significant influence on the rate of drug release, hardness, and elasticity of the film-coats.     

Fundamentals of Powder Compression. II. The Compression of Binary Powder Mixtures

Although tablet formulations are multicomponent systems, there have been only a few studies on the compression of binary or ternary powder mixtures. Physical interactions between the individual components may influence important biopharmaceutical properties of the compact, e.g., disintegration time and dissolution rate of the active ingredient. In the second part of this review paper the importance of these physical interactions is emphasized. The investigations are limited to the strength of the compact. An attempt is made to deduce additivity rules for the material-specific compressibility and compactibility parameters. Such additivity rules are of special importance, as they may allow the prediction of tablet properties at the formulation test. The final section is devoted to problems in compression, i.e., sticking and capping.     

Application of Thermodynamic Phase Diagrams and Gibbs Free Energy of Mixing for Screening of Polymers for Their Use in Amorphous Solid Dispersion Formulation of a Non-Glass-Forming Drug

The objective of the present investigations was to assess the use of thermodynamic phase diagrams and the Gibbs free energy of mixing, ΔG_mix, for the screening of the polymeric carriers by determining the ideal drug-loading for an amorphous solid dispersion formulation and optimum processing temperature for the hot-melt extrusion of a non-glass-forming drug. Mefenamic acid (MFA) was used as a model non-glass-forming drug and four chemically distinct polymers with close values of the solubility parameters, viz. Kollidon® VA64, Soluplus®, Pluronic® F68, and Eudragit® EPO, were used as carriers. The thermodynamic phase diagrams were constructed using the melting point depression data, Flory-Huggins theory, and Gordan-Taylor equation. The Gibbs free energy of mixing was estimated using the values of the drug-polymer interaction parameter, χ, and Flory-Huggins theory. The rank order miscibility of MFA in the four polymeric carriers estimated based on the difference in the values of their solubility parameters, Δδ, did not correlate well with the thermodynamic phase diagrams and Gibbs free energy plots. The study highlights the limitation of using the solubility parameter method in screening the polymeric carriers for poorly glass-forming drugs and reiterates the applicability of thermodynamic phase diagrams and Gibbs free energy plots in determining the ideal drug-loading and optimum processing temperature for hot-melt extrusion.     

Comparative evaluation of rate of hydration and matrix erosion of HEC and HPC and study of drug release from their matrices.

Hydrophilic polymers, in contact with the dissolution medium, may swell and make a continuous gel layer, erode or undergo combination of the two. The swelling action of these polymers is controlled by the rate of their hydration in the dissolution medium. The extent of polymer swelling, relative mobilities of dissolution medium and drug, and matrix erosion dictate the kinetics as well as mechanism of drug release from the polymeric matrices. The objective of the present investigations was to study the rate of hydration and the rate of matrix erosion of two hydrophilic, non-ionic cellulose ethers, i.e., hydroxyethylcellulose (HEC) and hydroxypropylcellulose (HPC), and to compare the kinetics and mechanism of drug release from their matrices. Chlorpheniramine maleate was used as the model drug. Matrix tablets containing chlorpheniramine maleate, HEC or HPC and dicalcium phosphate were compressed at 156 MPa pressure. The rate of hydration of the polymer, rate of erosion of the matrices and in vitro drug release studies were carried out in phosphate buffer (pH 7.4). The hydration studies of the two polymers demonstrated that due to relatively larger water uptake, the degree of swelling of HEC matrices was considerably higher as compared to the HPC matrices. Also, HEC matrices exhibited relatively higher erosion as compared to HPC matrices. The drug release from HEC matrices occurred by non-Fickian transport, i.e., combination of drug diffusion and polymer swelling, while drug release from HPC matrices was controlled primarily by diffusion through pores and channels in the structure. The t(50%), time to reach 50% drug release, for HEC matrices was 4.8 h and that for HPC matrices was 6.5 h which indicates that a higher polymer level was needed in the case of HEC matrices to sustain the drug release for up to 12 h of dissolution as compared to HPC matrices due to relatively higher hydrophilicity of HEC.     

Fundamentals of Powder Compression. I. The Compactibility and Compressibility of Pharmaceutical Powders

In spite of the widespread use of tablets, the theoretical understanding of the tableting process has been limited. During the last decades considerable research has been done in the field of powder technology and compaction. A survey of the literature and compression equations reveals many studies on the characterization of powder properties, most of which relate to volume reduction under pressure, i.e., to the compressibility of the powder bed. For practical purposes, however, it is also important to know the compactibility of a powder bed, i.e., the ability of a powdered material to be compressed into a compact of specified strength. This strength has to be defined, e.g., as radial tensile strength or deformation hardness. Thus the first part of this review comprises the theory of powder compression of individual substances, compression parameters, compression equations, and mechanical properties of compacts, including compact strength tests and compact hardness tests.     

Powdered Solution Technology: Principles and Mechanism

The concept of powdered solutions can be used to formulate liquid medications in dry, nonadherent, free-flowing, and readily compressible powders. The technique is based on simple admixture of drug solution or liquid drug with selected carrier and coating materials. Improved drug release profiles are exhibited by such delivery systems even for poorly water-soluble drugs. Previous work using this method has rendered its industrial application impractical because of the unsatisfactory flow properties of the powder admixtures. This article presents a theoretical model based on the principles and mechanism of powdered solutions and introduces a new physical property of powders termed the flowable liquid-retention potential ( value). Mathematical expressions are derived that can be used to calculate the optimum amount of excipients required to yield powder admixtures with acceptable flowability. The validity and applicability of these expressions have been verified experimentally using clofibrate and prednisolone as test materials. The proposed model is shown to be superior to previously reported studies in optimizing the amount of excipients needed to prepare powdered solutions with acceptable flow properties.