Browsing by Subject "Tablet"

Now showing 1 - 6 of 6
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    Development of Amorphous Solid Dispersion Tablet of Sorafenib with Improved Oral Bioavailability
    (2021-05) Song, Sichen
    An amorphous solid dispersion (ASD) immediate release tablet of sorafenib (SOR) was developed to improve oral bioavailability. The ASD was produced by coprecipitating both SOR and an enteric polymer, hydroxypropyl methylcellulose acetate succinate (HPMC-AS). The goal of maintaining supersaturation of ASDs was used to guide the selection of drug loading and HPMC-AS grade. The ASD of 40% drug loading with HPMC-AS M grade, which exhibits superior physical stability, enhanced dissolution extent and moderate hygroscopicity, was selected for further tablet development. Tablet formulation composition and dry granulation process were designed to achieve fast disintegration and adequate flow properties, and to mitigate over-granulation that would compromise in vivo performance. A material sparing and expedited approach was used to optimize compaction pressure to manufacture the ASD tablet with low friability and rapid disintegration. The resulting SOR ASD tablet showed enhanced in vitro dissolution rate and extent compared to the marketed product Nexavar®. A pharmacokinetic study in dogs suggested that the SOR ASD tablet exhibited a 1.5-fold improvement in the relative oral bioavailability compared to Nexavar®.
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    Enabling Direct Compression Tablet Development Of Celecoxib Through Solid State Engineering
    (2020-08) Wang, Kunlin
    Tablets are the most desirable solid oral dosage form for patients. Direct compression (DC) tablet formulation is the most economical, robust and efficient way of tablet manufacture. Being sensitive to properties of the Active Pharmaceutical Ingredient (API), direct compression tablet formulation is not available for the high dose non-steroidal anti-inflammatory drug, celecoxib (CEL) due to the undesirable properties of the commercial solid form of CEL, including low bulk density, poor flowability and tablet lamination issues. The solid form used in commercially available CEL capsules is a polymorph of CEL, Form III. Form III CEL is a needle shaped crystal, which is exceptionally elastic. This high elasticity, verified by nanoindentation and three-point bending tests, is unfavorable for good tablet quality and performance during high speed tableting. Through understanding the molecular interactions by analyzing the CEL crystal structure, a structural model for high elasticity is built and validated by Raman spectroscopy. Interlocked molecular packing without slip plane and the presence of isotropic hydrogen bond network are major structural features responsible for both the exceptional elastic flexibility and high stiffness of the CEL crystal. CEL Form III exhibits unsatisfactory flowability and tablet lamination issues for DC tablet manufacturing. Pharmaceutically acceptable solvates of CEL offer better flow, compaction and dissolution properties than CEL Form III. Two stoichiometric solvates of CEL and N-methyl-2-pyrrolidone (NMP) are extensively characterized and examined, which establishes a clear crystal structure-property relationship essential for crystal engineering of CEL. Through crystal engineering, a DC tablet formulation of CEL is successfully developed using the dimethyl sulfoxide (DMSO) solvate of CEL. This pharmaceutically acceptable solvate is highly stable and also exhibited much improved manufacturability compared to CEL Form III, including better flowability, lower elasticity and bulk density (superior tablet quality) as well as better dissolution performance. As a Class II drug in the biopharmaceutics classification system with low solubility and high permeability, the high dose of CEL is partially attributed to its limited solubility. Amorphous CEL, although providing solubility advantages as the thermodynamically high energy state, is unstable and prone to crystallization. The study of crystal growth of amorphous CEL reveals a fast glass-to-crystal growth mode at room temperature with a surface-enhanced mechanism. This paves the way for future development of a stable amorphous solid dispersion tablet product of CEL with improved dissolution performance and tablet manufacturability. In summary, by understanding the structural origin of undesired properties of CEL, successful development of the most patient-compliant tablet dosage form by direct compression can be achieved. This sets an excellent example of utilizing a solid state engineering approach to effectively overcome challenges encountered in direct compression tablet development.
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    In-Die Techniques to Characterize Powder Compression
    (2023-06) Vreeman, Gerrit
    Powder compaction plays a large role in many industries, including pharmaceutical tablet, metal part, detergent, cosmetics, and food manufacturing. Assessing the mechanical properties of a powdered material is an important step in developing processes that can effectively transform a powdered material into a product via densification. In-die analyses performed during compaction are fast and materials sparing compared to traditional out-of-die approaches. The goal of this work includes: (1) evaluate the effectiveness of fast, materials- sparing in-die methods for characterizing powder compaction compared to traditional out- of-die methods; (2) explore the benefits of using in-die elastic recovery measures to predict compact lamination via air entrapment; and (3) develop a universal compressibility model framework that can fully describe in-die compaction data, including all low- and high-pressure mechanisms. These goals aim to enable a fast and materials-sparing assessment of powder mechanical properties and lays a foundation for optimal formulation composition, processing strategy, and quality control assessment from such mechanical property assessments.
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    Lubrication In Pharmaceutical Tablet Manufacturing
    (2020-03) Dun, Jiangnan
    Appropriate compaction properties are critical to ensure a successful and robust tablet manufacture. According to Materials Science Tetrahedron (MST) theory, the quality of the tablet product is determined by the properties of pharmaceutical materials and the process conditions during manufacture. Lubricant, as one of the most important tablet excipients, has great impacts on the flow and mechanical properties of formulation. This work is heavily focused on understanding of the effects of process parameters on the lubrication as well as development of new lubricants for tablet formulation. Magnesium stearate, the most commonly used tablet lubricant, though exhibits excellent lubrication efficiency, leads to deterioration in tablet strength and dissolution. Sodium lauryl sulfate (SLS), Poloxamer 188 and Poloxamer 407 were selected as MgSt-alternative lubricants to be tested in tablet formulations. We found that the lubrication efficiency of these three materials are comparable with MgSt. More importantly, no significant tablet strength reduction was observed. Given to the higher hydrophilicity, tablets containing either of SLS, P188 or P407 showed enhanced dissolution profiles compared with MgSt containing tablets. Furthermore, robustness of formulation was remarkably improved when P188 or P407 was used as lubricant.
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    Modifying Pharmaceutical Properties of Levofloxacin by Crystal Engineering
    (2024-05) Huang, Pin-Syuan
    The commercial form of a fluoroquinolone antibiotic, levofloxacin (Lev), is a hydrochloride salt (Lev-HCl). Lev-HCl possesses an intense bitter taste, which presents a challenge for developing an oral tablet with high patient compliance. We approached this challenge by preparing a sweet salt of Lev with an artificial sweetener, Acesulfame (Acs), through an anion exchange reaction. Solid-state properties of an anhydrous Lev-Acs salt were characterized using various analytical techniques. With a degradation temperature at about 260 °C, Lev-Acs is thermally more stable than Lev-HCl. Lev-Acs also exhibits approximately 3 orders of magnitude lower aqueous solubility than Lev-HCl. Both the lower aqueous solubility and the presence of a sweetener make Lev-Acs an excellent candidate for taste-masking. Lev-Acs exhibits superior tabletability at pressures below 150 MPa, attributed to its high plasticity. The results suggest that Lev-Acs holds promise for formulating a palatable tablet, addressing challenges associated with Lev-HCl. Based on analysis of five pairs of stoichiometric hydrates and corresponding anhydrates, it was hypothesized that higher plasticity of a hydrate is caused by a lower crystal packing efficiency and density. In these systems, all hydrates exhibit higher plasticity and lower packing efficiency. Thus, an example of a hydrate with a higher packing efficiency exhibiting lower plasticity would strengthen this hypothesis. Ideally, this can be observed for channel hydrates, where filling the channel space by water molecules increases crystal packing efficiency. In the absence of such an ideal model system, we have tested this hypothesis using a channeled hemi-methanol solvate of a levofloxacin acesulfame salt. Our results confirm this hypothesis since, compared to the isostructural anhydrate, the hemi-methanol solvate exhibits higher packing efficiency and lower plasticity. The higher plasticity of the solvate is confirmed by both crystal structure analysis and energy framework calculations. If this correlation between crystal packing efficiency and plasticity is robust, we can objectively predict material plasticity of structurally related crystals based on crystal packing efficiency.
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    Perspectives of Special Educators on the Use of Tablets and Handhelds
    (2015-12) Curtis, Susan
    This paper presents the results of a mixed methods study on the use of tablets and handhelds in special education. The results identify the perceptions of 115 special educators representing 39 districts in Northwestern Wisconsin. This study examined the current and past practices of three groups of special educators. The study sought information regarding how special educators perceived changes to their technology practices as a result of their use of tablets and handhelds and how these changes benefited student learning. In addition, the study examined how the utilization of tablets and handhelds influenced the instruction and learning of students with disabilities (SWD) as well as the necessary school supports for the successful integration of assistive technology. Data from this study supported prior research identifying tablets and handhelds as valuable learning tools for SWD. This study presents a graphic framework that summarizes the data identifying the benefits of tablets and handhelds for student learning and instruction. Access is a key finding of this study. Special educator and student access to tablets and handhelds resulted in perceived student and educator benefits. Student benefits were noted in the areas of motivation, engagement, focus and attention, independence, communication, behavior, and social skills. Special educators and administrators report increased use of assistive technology, changes in how they differentiate, use instructional strategies, individualize, and group students for instruction after tablet and handheld use. The data from this study confirmed research on the importance of key school supports for successful technology integration in education. Identified are school and student success stories offering examples of tablet and/or handheld use in school contexts. Implications for practice provide suggestions that assist school districts and administrators to support tablet and handheld use in special education.