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French, Donna L.; Mauger, John W.

doi:10.1023/a:1018909527659

Cited by 78 publications

(25 citation statements)

References 10 publications

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“…The observed solubility of mesalazine in distilled water was in agreement with that reported in literature, being 0.84 mg/mL at 25 °C, and 1.41 mg/mL at 37 °C [20]. Reducing the pH to 1 also improved solubility [20]. However, the macrostructure of zein microparticles we formulated at pH 1 appeared hard and crystalline, as opposed to the soft coarse powder formed using a more neutral pH of 6.5 although the structure of zein is reportedly not affected in environments above pH 1 [21].…”

Section: Methodssupporting

confidence: 90%

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Encapsulation of Hydrocortisone and Mesalazine in Zein Microparticles

et al. 2013

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Zein was investigated for use as an oral-drug delivery system by loading prednisolone into zein microparticles using coacervation. To investigate the adaptability of this method to other drugs, zein microparticles were loaded with hydrocortisone, which is structurally related to prednisolone; or mesalazine, which is structurally different having a smaller LogP and ionizable functional groups. Investigations into the in vitro digestibility, and the electrophoretic profile of zein, and zein microparticles were conducted to shed further insight on using this protein as a drug delivery system. Hydrocortisone loading into zein microparticles was comparable with that reported for prednisolone, but mesalazine loading was highly variable. Depending on the starting quantities of hydrocortisone and zein, the average amount of microparticles equivalent to 4 mg hydrocortisone, (a clinically used dose), ranged from 60–115 mg, which is realistic and practical for oral dosing. Comparatively, an average of 2.5 g of microparticles was required to deliver 250 mg of mesalazine (a clinically used dose), so alternate encapsulation methods that can produce higher and more precise mesalazine loading are required. In vitro protein digestibility revealed that zein microparticles were more resistant to digestion compared to the zein raw material, and that individual zein peptides are not preferentially coacervated into the microparticles. In combination, these results suggest that there is potential to formulate a delivery system based on zein microparticles made using specific subunits of zein that is more resistant to digestion as starting material, to deliver drugs to the lower gastrointestinal tract.

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Section: Methodssupporting

confidence: 90%

“…Its solubility increased with an increase in temperature to 37 °C. The observed solubility of mesalazine in distilled water was in agreement with that reported in literature, being 0.84 mg/mL at 25 °C, and 1.41 mg/mL at 37 °C [20]. Reducing the pH to 1 also improved solubility [20].…”

Section: Methodssupporting

confidence: 88%

Encapsulation of Hydrocortisone and Mesalazine in Zein Microparticles

et al. 2013

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“…Diffusion coefficients of the drug/biologic fluid system were predicted using molecular dynamics simulation [9]. The dissolution parameters of the drug (c s and k) were obtained from literature [13].…”

Section: Mathematical Modelmentioning

confidence: 99%

Biological Variability and Targeted Delivery of Therapeutics for Inflammatory Bowel Diseases: An In Silico Approach

Haddish‐Berhane¹,

Farhadi²,

Nyquist³

et al. 2007

IADT

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Existing treatments of IBD adopt targeted oral drug delivery route for delivering bioactive agents more efficiently and with fewer side effects. However, the complex and dynamic luminal environment of the GIT and major intra/inter patient variability greatly affects treatment, resulting in variable clinical response in patients. Mathematical simulation model can be employed to consider the complex luminal environment to asses the performance of drug delivery systems for clinical efficacy. The objective of this paper was to evaluate existing targeted oral drug delivery system for the treatment of IBD subject to inter/intra patient luminal variability using in silico experiments employing previously developed mathematical model. Simulation results indicated that the average small intestinal drug release was 44+/-19% and 48+/-21% for healthy and UC subjects, respectively. The systemic absorption of drug approached 10-25% in healthy controls and 16-32% in UC subjects. Calculated drug release from the simulations for different scenario of pH and TT had a good agreement with the clinical in vivo data (13-36% and 17-35% for healthy and UC subjects, respectively). This agreement was also true for 5-ASA and its metabolite (N-acetyl-5-ASA) recovery in the colon. The computational model has a high degree of agreement with data obtained from literature. Physicians can use characteristic performance curves of different delivery systems produced in silico to select a delivery system that would work best for their patients based upon the patient's pH and transit time profiles. It also could be used by the pharmaceutical industry to improve their medicine efficacy by altering the design.

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“…Buffered aqueous medium affects the dissolution rate of a sparingly soluble weak acid or weak base drug due to ionic interactions between the drug and the buffer species in the microenvironment at the solid-liquid interface (5)(6)(7)(8)(9)(10)(11)(12)(13)(14); however, the influence of the buffer can be affected by the self-buffering capacity of the dissolved drug in the microenvironment. The extent to which the buffer influences dissolution rate depends on the ionization constants of the buffer and drug, total molar concentration of the buffer and buffer capacity, concentration of buffer species reacting with the drug compound, total drug solubility, and solubility of the un-ionized form of the drug compound.…”

Section: Introductionmentioning

confidence: 99%

Formulating Buffered Dissolution Media for Sparingly Soluble Weak Acid and Weak Base Drug Compounds Based on Microenvironmental pHo Considerations

Stippler¹,

Romero²,

Mauger³

2014

Dissolution Technol.

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The theoretical framework for dissolution of weak acid and weak base drug compounds in buffered media is well established. Therefore, this article is intended to provide a review of this framework and apply it to formulate buffered dissolution media based on ionic equilibrium conditions within the diffusion layer at the solid-liquid interface. The pH o in the microenvironment is identified as a singularly important parameter that reflects ionic interactions between dissolving drug and buffer at the solid-liquid interface. This article is focused on (1) formulating buffered dissolution media based on ionic equilibrium conditions at the solid-liquid interface, (2) identifying key physicochemical parameters for both drug and buffer that are relevant to buffer formulation, and (3) providing experimental and calculation-based methods to estimate the pH o at the solid-liquid interface. A shift in emphasis from relying solely on bulk buffer pH properties forms a basis for formulating buffered dissolution media and also provides insight into the physicochemical factors that affect the dissolution rate of the drug compound.

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Untitled

Cited by 78 publications

References 10 publications

Encapsulation of Hydrocortisone and Mesalazine in Zein Microparticles

Encapsulation of Hydrocortisone and Mesalazine in Zein Microparticles

Biological Variability and Targeted Delivery of Therapeutics for Inflammatory Bowel Diseases: An In Silico Approach

Formulating Buffered Dissolution Media for Sparingly Soluble Weak Acid and Weak Base Drug Compounds Based on Microenvironmental pHo Considerations

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