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Background/Objectives: Hydroxypropyl methylcellulose (HPMC) is one of the most commonly used hydrophilic polymers in formulations of matrix tablets for controlled release applications. However, HPMC attracts moisture and poses issues with drug stability in formulations containing moisture-sensitive drugs. Methods: Herein, the moisture sorption behavior of excipients and drug stability using aspirin as the model drug in matrix tablets were evaluated, using HPMC and the newly developed mannitol-coated HPMC, under accelerated stability conditions (40 °C, 75% relative humidity) with open and closed dishes. Results: Tablets prepared with mannitol-coated HPMC showed a slower drug degradation rate compared to tablets prepared with directly compressible HPMC. Initial moisture content and hygroscopicity were stronger predictors of drug stability compared to water activity when comparing samples without similar moisture content. In the early stage (day 0 to 30), the aspirin degradation rate was similar in both open and closed conditions, as moisture content is the main degradation contributor. In the later stage (day 30 to 90), aspirin degradation was faster under closed conditions than under open conditions, likely due to autocatalytic effects caused by the volatile acidic by-product entrapped in the closed environment. Conclusions: The findings from this study reinforced the importance of judicious excipient selection based on the understanding of excipient–moisture interactions to maximize the chemical stability of moisture-sensitive drugs. Mannitol-coated HPMC is a promising addition to the formulator's toolbox for the formulation of controlled release dosage forms by direct compression. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate paraffin wax as a potential controlled release matrix for spray congealing and its impact on drug release and stability of the microparticles. Paraffin wax can form a hydrophobic barrier to moisture and reduce drug degradation besides retarding drug release in the gastrointestinal tract. More hydrophilic lipid-based additives can be incorporated to modulate the drug release through the paraffin wax barrier. This study reports the findings of lipid–wax formulations at preserving the stability of moisture-sensitive drugs in spray-congealed microparticles. Aspirin-loaded microparticles formulated with different drug loads, lipid additives, and lipid:wax ratios were produced by spray congealing. Stearic acid (SA), cetyl alcohol (CA), and cetyl ester (CE) were the lipid additives studied. The microparticles were evaluated for yield, encapsulation efficiency, particle size, drug stability, and release. CE exhibited the greatest effect on increasing drug release, followed by CA and SA. Dissolution profiles showed the best fit to Weibull kinetic model. The degree of drug degradation was low, with CA imparting the least protective effect, followed by SA and CE. Paraffin wax is useful for preserving the stability of moisture-sensitive aspirin and retarding its release from spray-congealed microparticles. The addition of lipid additives modulated drug release without compromising drug stability. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The aim of this study was to evaluate how the addition of hydrophobic inclusions to sustained-release pellet film coat can affect drug release. Sustained-release formulations, in particular multiparticulate systems are gaining popularity because they are able to reduce the dosing frequency of drugs that require multiple dosing. In addition, the risk of dose dumping is low and local gastrointestinal irritation is minimised. Metformin-loaded pellets, prepared via extrusion-spheronisation, were coated with ethyl cellulose (EC)-based film coat, with and without hydrophobic inclusions to a series of coat thickness. Stearic acid 50 (SA) and hydrogenated castor oil (HCO) were the hydrophobic inclusions used. Drug release was investigated using the USP dissolution apparatus 2 and an ultraviolet imager. Release kinetics were analysed using the zero-order model. The physical properties of the pellets were characterised before and after dissolution. The addition of hydrophobic inclusions to EC-based film coat slowed down drug release, with SA slowing down drug release more than HCO. The influence of hydrophobic inclusions on drug release was clearly observable when the pellets were coated to 10% weight gain. It was postulated that the hydrophobic inclusions acted as physical barriers to increase the tortuosity of the diffusional path through the pellet film coat. The use of hydrophobic inclusions to control the rate of drug dissolution was shown to be promising. This could translate into potential cost and time savings with less materials and time used. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Knowledge on the dissolution behaviour of a drug is critical for efficient and effective product development. As the drug has almost always to be formulated with excipients in the design of a dosage form, it is important to examine the implications of the choice of excipients on the dissolution of the drug, among others, especially in the case of an immediate release dosage form. The objective of this study was to explore the potential of using an ultraviolet (UV) imaging technique to examine the effect of drug-excipient ratio on the initial dissolution of the drug, when formulated with a hydrophilic, water insoluble excipient. A series of drug-excipient binary blends with different ratios were prepared and compacted into 2 mm compacts, and their dissolution profiles captured with a UV imager. Chemical imaging via Raman spectroscopy was also performed on the compacts to quantify the fraction of drug presented on the compact surface. At low drug concentrations, a suppression in drug dissolution was observed, but beyond a critical drug-excipient ratio, the concentration of the excipient no longer played a role in affecting drug dissolution rates. Drug particle size was found to affect the critical drug-excipient ratio required to negate the shielding effect exerted by the excipient, such that a higher proportion of drug was required. It is postulated that the excipient served as a physical barrier, as well as competitor for water required for wetting during initial dissolution, thereby causing a delay in the wetting and dissolution of the drug. [ABSTRACT FROM AUTHOR]

Crospovidone is a commonly used tablet disintegrant. However, the synthetic disintegrant has been known to be hygroscopic and high moisture content in crospovidone used could exert deleterious effects on tablets formulated with it. The objective of this study was to elicit a better understanding between crospovidone-water interaction and its effect on disintegrant performance. Moisture sorption and desorption isotherms were obtained together with the enthalpy of immersion. Crospovidone samples stored at four relative humidities were used to formulate tablets and the resultant tablets were evaluated for their mechanical, dimensional and disintegratability attributes. Analyses of the moisture sorption isotherms indicated that externally adsorbed moisture accounted for the bulk of the total moisture content in crospovidone, with minimal amount of moisture absorbed intramolecularly. Enthalpy of immersion became less exothermic with crospovidone samples stored at increasing storage humidity. Correspondingly, improvement in disintegration time became less pronounced. This was postulated to be a consequence of premature wetting of the particle surfaces by externally adsorbed moisture. High humidity was also detrimental to tablet hardness and thickness. In conclusion, the impact of moisture sorption during storage by excipients such as crospovidone could be better understood by the appreciation of crospovidone-water interaction and its consequence on tablet quality. [ABSTRACT FROM AUTHOR]

[Display omitted] One of the most common forms of controlled release technology for oral drug delivery comprises an active ingredient dispersed in a hydrophilic matrix forming polymer such as hydroxypropyl methylcellulose (HPMC), which is tableted via direct compression. However, HPMC may pose problems in direct compression due to its poor flowability. Hence, mannitol syrup was spray-coated over fluidized HPMC particles to produce co-processed HPMC–mannitol at ratios of 20:80, 50:50, and 70:30. Particles of pure HPMC, co-processed HPMC–mannitol, and their respective physical mixtures were evaluated for powder flowability, compression profiles, and controlled release performance. It was found that co-processed HPMC–mannitol consisted of particles with improved flow compared to pure HPMC particles. Sufficiently strong tablets of >2 MPa could be produced at moderate to high compression forces of 150–200 MPa. The dissolution profile could be tuned to obtain desired release profiles by altering HPMC–mannitol ratios. Co-processed HPMC–mannitol offers an interesting addition to the formulator's toolbox in the design of controlled release formulations for direct compression. [ABSTRACT FROM AUTHOR]

Amorphous solid dispersions (ASDs) are of great interest due to their ability to enhance the delivery of poorly soluble drugs. Recent studies have shown that, in addition to acting as a crystallization inhibitor, the polymer in an ASD plays a role in controlling the rate of drug release, notably in congruently releasing formulations, where both the drug and polymer have similar normalized release rates. The aim of this study was to compare the solid-state stability and release performance of ASDs when formulated with neutral and enteric polymers. One neutral (polyvinylpyrrolidone-vinyl acetate copolymer, PVPVA) and four enteric polymers (hypromellose acetate succinate; hypromellose phthalate; cellulose acetate phthalate, CAP; methacrylic acid-methyl methacrylate copolymer, Eudragit L 100) were used to formulate binary ASDs with lumefantrine, a hydrophobic and weakly basic antimalarial drug. The normalized drug and polymer release rates of lumefantrine-PVPVA ASDs up to 35% drug loading (DL) were similar and rapid. No drug release from PVPVA systems was detected when the DL was increased to 40%. In contrast, ASDs formulated with enteric polymers showed a DL-dependent decrease in the release rates of both the drug and polymer, whereby release was slower than for PVPVA ASDs for DLs < 40% DL. Drug release from CAP and Eudragit L 100 systems was the slowest and drug amorphous solubility was not achieved even at 5% DL. Although lumefantrine-PVPVA ASDs showed fast release, they also showed rapid drug crystallization under accelerated stability conditions, while the ASDs with enteric polymers showed much greater resistance to crystallization. This study highlights the importance of polymer selection in the formulation of ASDs, where a balance between physical stability and dissolution release must be achieved.