The influence of polymer content on early gel-layer formation in HPMC matrices: The use of CLSM visualisation to identify the percolation threshold

Mason, Laura; Campiñez, María Dolores; Pygall, Samuel R.; Burley, J.; Gupta, Pramod; Storey, David; Caraballo, Isidoro; Melia, Colin D.

doi:10.1016/j.ejpb.2015.06.019

Cited by 22 publications

(7 citation statements)

References 36 publications

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“…A recent study has provided additional insight on gel layer formation in hydrophilic matrices through direct observation using confocal laser scanning fluorescence microscopy (Mason, 2015). The findings of this study provide direct evidence of how percolation threshold may be linked to the success or failure of early gel layer formation in hydrophilic (HPMC) matrices.…”

Section: Discussionmentioning

confidence: 69%

A challenge-based laboratory to explore drug delivery from swellable matrices

Farrell

Vernengo

2016

Education for Chemical Engineers

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This paper describes an experiment that introduces students to drug delivery from swellable matrices (tablets). Students produce hydrophilic polymeric tablets loaded with drug and measure the rate of release from the tablets for systems having different drug loading, polymer composition and polymer molecular weight. Transient concentration data are obtained from drug release studies and analyzed to characterize the release profile and to determine the predominant rate controlling mechanism. The purpose of the experiment is to provide engineering students with basic skills relevant to drug delivery while simultaneously introducing or reinforcing science principles; applications of science, math and engineering; the science and art of design, and data analysis. Students showed significant pre-post gains in several areas, and the gains for each objective between the pre-and post-test ranged from 48-60%. The average normalized gain between pre-test and post-test was 65%.

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Section: Discussionmentioning

confidence: 69%

A challenge-based laboratory to explore drug delivery from swellable matrices

Farrell

Vernengo

2016

Education for Chemical Engineers

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“…Alternatively, formulations containing lactose (F4 and F6) showed the highest release, which can be attributed to the water solubility of lactose. The slowest release of DSV was from matrices containing maltodextrin (F1, F4) possibly due to the small aqueous pores found in case of maltodextrin due to gel formation upon contact with water, which can form coherent diffusion barrier that delays further percolation of the hydration medium (Chronakis, 1998, Levina and Rajabi-Siahboomi, 2004, Mason et al, 2015). It has been reported that modified starches (maltodextrins) could be used efficiently in the reduction of drug release rate from controlled release tablets because of their cold water-swelling capacity forming gel barrier (Bravo et al, 2002, Nickerson et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

“…A rapid formation of this gelatinous layer is critical to prevent wetting of the interior and disintegration of the tablet core. Once the original protective gel layer was formed, it controls the penetration of additional water into the tablet (Mason et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets

Samy

Elnoby

El‐Gowelli

et al. 2017

Saudi Pharmaceutical Journal

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Desvenlafaxine succinate (DSV) is a water soluble anti-depressant drug, which is rapidly absorbed after oral administration exaggerating its side effects. The current work aimed to prepare controllable release DSV matrix to reduce DSV side effects related to its initial burst. Fifteen DSV matrix formulations were prepared using different polymers, polymer/drug ratios and matrix excipients and characterized using Differential Scanning Calorimetry (DSC), infrared (IR) spectroscopy, water uptake and DSV release. The release kinetics were calculated to determine the drug release mechanism. DSV absorption via rat intestinal mucosal cells and the calculation of the apparent permeability coefficient (P) were performed using everted sac technique. Maltodextrin was the best matrix excipient (F7 and F10) showing acceptable decrease in the initial burst compared to the innovator. The addition of negatively charged polymers sodium carboxy methyl cellulose (SCMC) or sodium alginate resulted in an interaction that was proved by DSC and IR findings. This interaction slowed DSV release. F10 showed an excellent absorption of more than 80% of DSV after 4 h and the highest similarity factor with the innovator (84.7). A controllable release pattern of DSV was achieved using Methocel, Maltodextrin and SCMC. The obtained results could be used as a platform to control the release of cationic water soluble drugs that suffer from side effects associated with their initial burst after oral administration.

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“…The decrease in drug apparent solubility by HPMC presence was more pronounced at early time points. When HPMC is used at low levels (< 10% w/w) in tablet formulations, a heterogeneous viscous HPMC layer is formed initially and cannot be maintained due to water penetration (19). Therefore, the higher reduction in drug apparent solubility at early compared to late time points may be explained by the disruption of the gel layer by water molecules.…”

Section: Impact Of Excipients On Drug Solubility Based On Excipient Pmentioning

confidence: 99%

“…Use of confocal laser scanning microscopy revealed that the early gel layer formation depends on the level of HPMC. Hydrophilic matrices containing 5% w/w and 10% w/w of HPMC formed a thin and heterogeneous gel layer initially (5-15 min), which could not be maintained due to the increased water uptake accelerating polymer erosion (19).…”

Section: Introductionmentioning

confidence: 99%

Biopharmaceutical Understanding of Excipient Variability on Drug Apparent Solubility Based on Drug Physicochemical Properties: Case Study—Hypromellose (HPMC)

Zarmpi

Flanagan

Meehan³

et al. 2020

AAPS J

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Identification of the biopharmaceutical risks of excipients and excipient variability on oral drug performance can be beneficial for the development of robust oral drug formulations. The current study investigated the impact of Hypromellose (HPMC) presence and varying viscosity type, when used as a binder in immediate release formulations, on the apparent solubility of drugs with wide range of physicochemical properties (drug ionization, drug lipophilicity, drug aqueous solubility). The role of physiological conditions on the impact of excipients on drug apparent solubility was assessed with the use of pharmacopoeia (compendial) and biorelevant media. Presence of HPMC affected drug solubility according to the physicochemical properties of studied compounds. The possible combined effects of polymer adsorption (drug shielding effect) or the formation of a polymeric viscous layer around drug particles may have retarded drug dissolution leading to reduced apparent solubility of highly soluble and/or highly ionized compounds and were pronounced mainly at early time points. Increase in the apparent solubility of poorly soluble low ionized drugs containing a neutral amine group was observed which may relate to enhanced drug solubilization or reduced drug precipitation. The use of multivariate data analysis confirmed the importance of drug physicochemical properties on the impact of excipients on drug apparent solubility and revealed that changes in HPMC material properties or amount may not be critical for oral drug performance when HPMC is used as a binder. The construction of a roadmap combining drug, excipient, and medium characteristics allowed the identification of the cases where HPMC presence may present risks in oral drug performance and bioavailability.

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The influence of polymer content on early gel-layer formation in HPMC matrices: The use of CLSM visualisation to identify the percolation threshold

Cited by 22 publications

References 36 publications

A challenge-based laboratory to explore drug delivery from swellable matrices

A challenge-based laboratory to explore drug delivery from swellable matrices

Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets

Biopharmaceutical Understanding of Excipient Variability on Drug Apparent Solubility Based on Drug Physicochemical Properties: Case Study—Hypromellose (HPMC)

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