ABSTRACT
The tableting of most pharmaceutical formulations requires the addition of lubricants to reduce ejection forces, prevent tooling damage and tablet defects. The internal addition of lubricants is known to reduce tablet tensile strength, especially of mainly plastically deforming materials. To date, available models show only limited quantitative predictive accuracy for the influence of lubricant concentration on the mechanical strength of tablets. This study aims to fill this gap and present a model based on the Ryshkewitch-Duckworth equation that can estimate the compactibility profiles of lubricated formulations. Binary mixtures of different diluents (microcrystalline cellulose and lactose) were prepared with common lubricants (magnesium stearate and sodium stearyl fumarate) and subsequently tableted. The resulting compactibility profiles were fitted using the Ryshkewitch-Duckworth equation and the derived fit parameters (kb and σ0) were correlated with the lubricant concentration. Subsequently, an empirical model was established which requires a minimum of experimental data and is able to predict the tensile strength of lubricated diluent tablets. Consequently, the developed empirical model is an interesting and valuable addition to the existing multi-component compacting models available and offers the opportunity to accelerate experimentation in the development of new tablet formulations.
Subject(s)
Excipients , Stearic Acids , Drug Compounding , Excipients/chemistry , Lubricants/chemistry , Lubrication , Stearic Acids/chemistry , Tablets , Tensile StrengthABSTRACT
The aim of the present work was to evaluate the viability of a time-dependent delivery platform (Chronotopic) in preparing an insulin-based system intended for oral colon delivery. The main objectives were to assess the influence of the manufacturing process and storage conditions on the protein stability. Insulin-loaded cores were manufactured by direct compression and were subsequently coated with hydroxypropyl methylcellulose (HPMC) in a top-spray fluid bed up to increasing weight gains, namely 20%, 60% and 100%. In order to evaluate the impact the operating conditions may have on the protein integrity, insulin and its main degradation products (A21-desamido insulin -A21, Other Insulin-Related Compounds -OIRCs, and High-Molecular Weight Proteins -HMWPs) were assayed on samples collected after each process step by chromatographic methods. Furthermore, long-term (4 degrees C) and accelerated (25 degrees C-60% RH) stability studies were carried out on tablet cores and coated systems by assessing insulin, A21, OIRC and HMWP percentages throughout a one-year storage period. In addition, the in vitro release behaviour was investigated during the same study period. The overall results indicated that the manufacturing process is not detrimental for insulin integrity and that 4 degrees C storage temperature alters neither the protein content nor the release performances of the device. It was therefore concluded that insulin-containing systems intended for oral colon delivery can be obtained by the Chronotopic technology.
Subject(s)
Administration, Oral , Colon/drug effects , Insulin Infusion Systems , Animals , Cattle , Chemistry, Pharmaceutical/methods , Drug Carriers/metabolism , Drug Compounding , Drug Delivery Systems , Insulin/administration & dosage , Models, Statistical , Solubility , Tablets , Technology, Pharmaceutical/methods , Temperature , Time FactorsABSTRACT
The aim of the study was to provide a controlled release system, which could be used for the oral administration of highly water-insoluble drugs. Pellets have been prepared by extrusion/spheronization containing two model drugs (methyl and propyl parabens) of low water solubility. One type of pellets contained the drugs mixed with lactose and microcrystalline cellulose (MCC) and the other types of pellets contained the model drugs dissolved in a self-emulsifying system (4.8%) consisting of equal parts of mono-diglycerides and polysorbate 80 and MCC. Pellets of all types in the same size fraction (1.4-2.0 mm) were coated to different levels of weight gain, with ethylcellulose, talc and glycerol. A sample of pellets containing methyl parabens in the self-emulsifying system was pre-coated with a film of hydroxypropylmethyl cellulose from an aqueous solution and then coated as above. Dissolution experiments established that the presence of the self-emulsifying system enhanced the drug release of both model drugs and that the film coating considerably reduced the drug release from pellets made with just water, lactose and MCC. The coating reduced the drug release from the pellets containing the self-emulsifying system to a lesser extent but in relation to the quantity of coat applied to the pellets. The application of a sub-coating of hydroxypropylmethyl cellulose was able to reduce the release rate of methyl parabens self-emulsifying system ethyl cellulose coated pellets. Thus, the formulation approach offers the possibility of formulating and controlling the in vitro release of water-insoluble drugs from solid oral dosage forms.
