Multiscale Relaxation Behavior of Amorphous Plasticized Poly(vinyl butyral).

As a key component in laminated glass, plasticized polyvinyl butyral (PVB) interlayer is a kind of impact-resistant polymer material with high toughness. Recently, by using ultrasmall angle X-ray scattering (USAXS) technique, Stretch-induced phase-separated structure on the scale of hundreds of nanometers formed in plasticized PVB for the first time is reported. In this work, the multiscale relaxation behavior of plasticized PVB is further investigated. The relaxation behavior of deformed plasticized PVB is studied from macroscopic stress, mesoscopic phase-separated structure, and microscopic chain segment by combining USAXS, and birefringence with in situ stretching device. The contributions of chain segments and hydrogen bonding clusters for the multiscale relaxation behavior are discussed.

Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets.

PURPOSE: To investigate the influence of the pH of the dissolution medium on immediate release 850 mg metformin hydrochloride tablets. METHODS: A traditional wet granulation method was used to manufacture metformin hydrochloride tablets with or without a disintegrant. Tablet dissolution was conducted using the USP apparatus I at 100 rpm. RESULTS: In spite of its pH-independent high solubility, metformin hydrochloride tablets dissolved significantly slower in 0.1 N HCl (pH 1.2) and 50 mM pH 4.5 acetate buffer compared with 50 mM pH 6.8 phosphate buffer, the dissolution medium in the USP. Metformin hydrochloride API compressed into a round 1200 mg disk showed a similar trend. When basket rotation speed was increased from 100 to 250 rpm, the dissolution of metformin hydrochloride tablets was similar in all three media. Incorporation of 2% w/w crospovidone in the tablet formulation improved the dissolution although the pH-dependent trend was still evident, but incorporation of 2% w/w croscarmellose sodium resulted in rapid pH-independent tablet dissolution. CONCLUSION: In absence of a disintegrant in the tablet formulation, the dissolution was governed by the erosion-diffusion process. Even for a highly soluble drug, a super-disintegrant was needed in the formulation to overcome the diffusion layer limitation and change the dissolution mechanism from erosion-diffusion to disintegration.

An active film-coating approach to enhance chemical stability of a potent drug molecule.

Peliglitazar, a PPAR α/γ agonist, was found to undergo acid as well as base catalyzed degradation. The acid catalyzed degradation led to the formation of benzylic alcohol and glycine carbamate and the base catalyzed degradation led to formation of p-hydroxyanisole and an amine degradant. In capsule formulations, the capsules with the lowest drug-loading exhibited maximum instability even at 25 °C/60% RH storage condition. Incorporation of pH-modifiers to maintain 'micro-environmental pH' acidic did not prevent the formation of the base-catalyzed degradants. Traditional dry granulated tablet formulation which is qualitatively similar to the capsule formulations showed the presence of acid-catalyzed degradants even without the presence of an acidifying agent. On the other hand, traditional wet granulated tablet formulation showed mainly base-catalyzed degradants. Stability problems of the tablet formulation were aggravated because the potent molecule required low tablet strengths which resulted in low drug to excipient ratio. To stabilize the molecule, an active film-coating approach was explored. In this approach, the drug was sprayed with the coating material onto non-active containing tablet cores. This approach of trapping the drug particles into the coating material provided tablets with satisfactory chemical stability. The stability enhancement observed in the active coating approach is attributed to the higher drug to excipient ratio in the film coat of non-reactive coating material compared to that in the traditional dry or wet granulated formulations.

Surfactant-mediated dissolution of metformin hydrochloride tablets: wetting effects versus ion pairs diffusivity.

The aqueous solubility of metformin (pKa: 2.8 and 11.5) in the pH range of 1.2-6.8 is 300 mg/mL. Thus, the dissolution of metformin hydrochloride tablets should be pH independent. However, 850 mg metformin hydrochloride tablets dissolved more slowly in pH 1.2 and 4.5 dissolution media than in pH 6.8 medium. It is hypothesized that the additional protonation of metformin at the acidic pH results in higher solvation and a larger hydrodynamic radius, leading to slower diffusion and dissolution. This hypothesis was supported by the observation that cationic metformin and anionic sodium lauryl sulfate (SLS), 0.1% (w/v), formed an insoluble salt (1:2 molar ratio) at pH 1.2 and 4.5, but not at pH 6.8. SLS at 0.01% (w/v) in all three media enhanced metformin dissolution. The slower metformin dissolution at pH 1.2 and 4.5 media with SLS can be attributed to the formation of metformin-lauryl sulfate (Met-LS) (1:2 and 1:1) ion pairs, which are more hydrophobic than Met-LS (1:1) ion pairs at pH 6.8. Slower metformin diffusivity in pH 4.5 with 0.05% (w/v) SLS was observed by diffusion-ordered spectroscopy nuclear magnetic resonance. Improved metformin wetting by SLS outweighed the lower diffusivity of metformin-LS ion pairs because similar enhancement in dissolution was noted with 0.5% (w/v) nonionic polysorbate 80.

Effect of human serum albumin on cell attachment of human gingival epithelial cells.

OBJECTIVE: To investigate the effect of human serum albumin (HSA) on cell attachment of human gingival epithelial cells (HGE). METHODS: HGE were primary cultured with keratinocyte serum-free medium (KSFM) and dispase. The cultured cells were immunohistochemically stained by monoclonal anti-pan cytokeratin. MTT test was employed to investigate the influence of HSA on the cell attachment on polystyrene surface. The cell growth curve of HGE which were cultured in KSFM with 50 g/L HSA was observed. RESULTS: The results showed significant decrease in cell numbers within 8 hours after HGE were inoculated, in which the polystyrene surface was preincubated with 50 g/L HSA. But it did not prove to be the case from 10 hours to 24 hours after HGE were inoculated. There were no significant difference within 24 hours in cell numbers between cultured in KSFM with 50 g/L HSA and control. The cell numbers in cell growth curve of HGE in KSFM with and without 50 g/L HSA did not show significant difference. CONCLUSIONS: HSA preincubation on polystyrene were produce inhibitory effect of HGE attachment in early stage.