Comparison of US Pharmacopeia Simulated Intestinal Fluid TS (without pancreatin) and Phosphate Standard Buffer pH 6.8, TS of the International Pharmacopoeia with Respect to Their Use in In Vitro Dissolution Testing

Stippler, Erika; Kopp, Sabine; Dressman, Jennifer B.

doi:10.14227/dt110204p6

Cited by 78 publications

(48 citation statements)

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“…Although the buffer capacity of the 0.05 M phosphate buffer (IntPh3) was slightly higher than that of SIFsp, no difference in the dissolution profiles was observed. This is consistent with a previous study by Dressman et al who found that SIFsp could be used interchangeably with 0.05 M phosphate buffer (IntPh3) in the dissolution testing of immediaterelease dosage forms (37). Overall, acetate buffer and blank FeSSIF allowed for higher dissolution rate than blank FaSSIF, SIFsp, and 0.05 M phosphate buffer (IntPh3).…”

Section: Dissolution Studiessupporting

confidence: 92%

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

et al. 2015

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Abstract. The objective of this study was to investigate the pH-dependent solubility and dissolution of weakly basic Biopharmaceutical Classification Systems (BCS) class II drugs, characterized by low solubility and high permeability, using carvedilol, a weak base with a pK a value of 7.8, as a model drug. A series of solubility and in vitro dissolution studies was carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH range of the GI from 1.2 to 7.8. The effect of ionic strength, buffer capacity, and buffer species of the dissolution media on the solubility and dissolution behavior of carvedilol was also investigated. The study revealed that carvedilol exhibited a typical weak base pH-dependent solubility profile with a high solubility at low pH (545.1-2591.4 μg/mL within the pH range 1.2-5.0) and low solubility at high pH (5.8-51.9 μg/mL within the pH range 6.5-7.8). The dissolution behavior of carvedilol was consistent with the solubility results, where carvedilol release was complete (95.8-98.2% released within 60 min) in media simulating the gastric fluid (pH 1.2-5.0) and relatively low (15.9-86.2% released within 240 min) in media simulating the intestinal fluid (pH 6.5-7.8). It was found that the buffer species of the dissolution media may influence the solubility and consequently the percentage of carvedilol released by forming carvedilol salts of varying solubilities. Carvedilol solubility and dissolution decreased with increasing ionic strength, while lowering the buffer capacity resulted in a decrease in carvedilol solubility and dissolution rate.

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Section: Dissolution Studiessupporting

confidence: 92%

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

et al. 2015

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“…26 An excess of RTV was added into 5 mL of a medium and stirred for 48 hours at 37°C. Then, 1 mL of the suspension was centrifuged at 14,000 rpm for 10 minutes at room temperature, and the supernatant was taken.…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability

Guo

Pham

et al. 2016

IJN

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Purpose The purpose of this study was to develop a novel lipid-based nanotechnology to formulate poorly water-soluble drugs in oral solid granules to improve stability, palatability, and bioavailability. Materials and methods In one method, we prepared ritonavir (RTV) nanoparticles (NPs) by a microemulsion-precursor method and then converted the RTV NPs to solid granules by wet granulation to produce RTV NP-containing granules. In the other innovative method, we did not use water in the formulation preparation, and discovered novel in situ self-assembly nanoparticles (ISNPs). We prepared RTV ISNP granules that did not initially contain NPs, but spontaneously produced RTV ISNPs when the granules were introduced to water with gentle agitation. We fully characterized these RTV nanoformulations. We also used rats to test the bioavailability of RTV ISNP granules. Finally, an Astree electronic tongue was used to assess the taste of the RTV ISNP granules. Results RTV NP-containing granules only had about 1% drug loading of RTV in the solid granules. In contrast, RTV ISNP granules achieved over 16% drug loading and were stable at room temperature over 24 weeks. RTV ISNPs had particle size between 160 nm and 300 nm with narrow size distribution. RTV ISNPs were stable in simulated gastric fluid for 2 hours and in simulated intestinal fluid for another 6 hours. The data from the electronic tongue showed that the RTV ISNP granules were similar in taste to blank ISNP granules, but were much different from RTV solution. RTV ISNP granules increased RTV bioavailability over 2.5-fold compared to RTV solution. Conclusion We successfully discovered and developed novel ISNPs to manufacture RTV ISNP granules that were reconstitutable, stable, and palatable, and improved RTV bioavailability. The novel ISNP nanotechnology is a platform to manufacture oral solid dosage forms for poorly water-soluble drugs, especially for pediatric formulation development.

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“…However, as shown by Stippler et al, these buffers have similar properties including osmolality, ionic strength, and buffer capacity (72). In the same study, the media were considered interchangeable in the dissolution testing of ibuprofen, metronidazole, and indomethacin immediate-release solid oral dosage form.…”

Section: Usp Compendial Mediamentioning

confidence: 95%

Evolution of Choice of Solubility and Dissolution Media After Two Decades of Biopharmaceutical Classification System

Bou‐Chacra

Melo

Morales

et al. 2017

AAPS J

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Abstract.The introduction of the biopharmaceutics drug classification system (Biopharmaceutics Classification System (BCS)), in 1995, provided a simple way to describe the biopharmaceutics behavior of a drug. Solubility and permeability are among the major parameters, which determine the fraction dose absorbed of a drug substance and consequently its chances to be bioavailable. The purpose of this review is to summarize the evolution of the media used for determining solubility and dissolution and how this can be used in modern drug development. Over the years, physiologically adapted media and buffers were introduced with the intention to better predict the in vivo solubility and dissolution of drug substances. Water, buffer solutions, compendial media, micellar solubilization media, and biorelevant media are reviewed. At this time point, there is no universal medium available which can be used to predict every drug substance's solubility or a drug product's in vivo dissolution behavior. However, there have been many improvements and additions made to media to optimize their in vivo predictability; for example, the current phosphate concentrations in buffers seem to be too high to correlate with the carbonate buffer concentrations in vivo. Biorelevant media were updated to correlate them better with the composition of human intestinal fluids. The BCS was introduced into regulatory sciences as a scientific risk management tool to waive bioequivalence studies under certain conditions. Today's different guidance documents define the dose-solubility ratio differently. As shown for amoxicillin, this can cause more confusion than certainty for globally operating companies. Harmonization of BCS guidelines is highly desirable.

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Comparison of US Pharmacopeia Simulated Intestinal Fluid TS (without pancreatin) and Phosphate Standard Buffer pH 6.8, TS of the International Pharmacopoeia with Respect to Their Use in In Vitro Dissolution Testing

Cited by 78 publications

References 0 publications

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability

Evolution of Choice of Solubility and Dissolution Media After Two Decades of Biopharmaceutical Classification System

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Comparison of US Pharmacopeia Simulated Intestinal Fluid TS (without pancreatin) and Phosphate Standard Buffer pH 6.8, TS of the International Pharmacopoeia with Respect to Their Use in In Vitro Dissolution Testing

Cited by 78 publications

References 0 publications

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

pH-Dependent Solubility and Dissolution Behavior of Carvedilol—Case Example of a Weakly Basic BCS Class II Drug

Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and&nbsp;bioavailability

Evolution of Choice of Solubility and Dissolution Media After Two Decades of Biopharmaceutical Classification System

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Product

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Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability