Search Results (3)

The transition from batch to continuous processes in the pharmaceutical industry has been driven by the potential improvement in process controllability, product quality homogeneity, and reduction of material inventory. A quality-by-control (QbC) approach has been implemented in a variety of pharmaceutical product manufacturing modalities to increase product quality through a three-level hierarchical control structure. In the implementation of the QbC approach it is common practice to simplify control algorithms by utilizing linearized models with constant model parameters. Nonlinear model predictive control (NMPC) can effectively deliver control functionality for highly sensitive variations and nonlinear multiple-input-multiple-output (MIMO) systems, which is essential for the highly regulated pharmaceutical manufacturing industry. This work focuses on developing and implementing NMPC in continuous manufacturing of solid dosage forms. To mitigate control degradation caused by plant-model mismatch, careful monitoring and continuous improvement strategies are studied. When moving horizon estimation (MHE) is integrated with NMPC, historical data in the past time window together with real-time data from the sensor network enable state estimation and accurate tracking of the highly sensitive model parameters. The adaptive model used in the NMPC strategy can compensate for process uncertainties, further reducing plant-model mismatch effects. The nonlinear mechanistic model used in both MHE and NMPC can predict the essential but complex powder properties and provide physical interpretation of abnormal events. The adaptive NMPC implementation and its real-time control performance analysis and practical applicability are demonstrated through a series of illustrative examples that highlight the effectiveness of the proposed approach for different scenarios of plant-model mismatch, while also incorporating glidant effects. Full article

Glidants and lubricants are often used to modify interparticle friction and adhesion in order to improve powder characteristics, such as flowability and compactability. Magnesium stearate (MgSt) powder is widely used as a lubricant. Shear straining causes MgSt particles to break, delaminate, and adhere to the surfaces of the host particles. In this work, a comparison is made of the effect of three mixer types on the lubricating role of MgSt particles. The flow behaviour of α-lactose monohydrate, coated with MgSt at different mass percentages of 0.2, 0.5, 1, and 5 is characterised. The mixing and coating process is carried out by dry blending using Turbula, ProCepT, and Mechanofusion. Measures have been taken to operate under equivalent mixing conditions, as reported in the literature. The flow resistance of the coated samples is measured using the FT4 rheometer. The results indicate that the flow characteristics of the processed powders are remarkably similar in the cases of samples treated by Turbula and Mechanofusion, despite extreme conditions of shear strain rate. The least flow resistance of samples is observed in the case of samples treated by the ProCepT mixer. High-velocity collisions of particles round off the sharp corners and edges, making them less resistant to flow. The optimal percentage of magnesium stearate is found to be approximately 1% by weight for all mixer types, as the addition of higher amounts of lubricant does not further improve the flowability of the material. Full article

Dysphagia refers to difficulty swallowing certain foods, liquids, or pills. It is common among the elderly with chronic diseases who need to take drugs for long periods. Therefore, dysphagia might reduce compliance with oral drug administration in the aging population. Many pharmaceutical companies search for new products to serve as swallowing aids. Existing products are expensive and do not suit all geriatric patients. Therefore, this study aimed to develop and investigate pill swallowing aid gels prepared from carboxymethyl cellulose and chitosan. We formulated gels by dissolving different concentrations of carboxymethyl cellulose and low or high molecular weight chitosan in solvents to find appropriate gel rheology properties. We then added several portions of glycerin as the glidant of the formulation. We found that the optimized gel formulation was 6.25% (w/w) chitosan with a molecular weight of 80–120 kDa dissolved in 1.2% acetic acid and 4% (w/w) glycerin. The developed pill swallowing gel’s rheology was pseudoplastic with a viscosity of 73.74 ± 3.20 Pa⸱s. The developed chitosan gel had enhanced flow ability; it allowed the pill to cross a 300 mm tube within 6 s, while the reference product took 3 s. Even though the reference product could carry the pill in the tube faster, the chitosan gel better covered the pill, making it more convenient to use. Finally, using a theophylline tablet as a model tablet dosage form, we assessed the gel’s effect on drug disintegration and dissolution. The chitosan gel delayed the tablet disintegration time by about 3–7 min and slightly affected the theophylline dissolution rate. Lastly, all gels were physically stable after a month of storage in the stress condition. These results show the feasibility of manufacturing a chitosan gel usable as a pill swallowing gel for patients with dysphagia. Full article