Generic omeprazole delayed-release capsules: in vitro performance evaluations

Moore, Terry W.; Smith, Anjanette P.; Ye, Wei; Toler, Duckhee Y.; Westenberger, Benjamin J.; Lionberger, Robert; Raw, Andre; Yu, Lawrence X.; Buhse, Lucinda F.

doi:10.1080/03639040802698802

Cited by 12 publications

(11 citation statements)

References 2 publications

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“…9 However, it should be noted that in a study evaluating 5 generic omeprazole products in the United States, all 5 products met the in vitro drug dissolution standards established by the United States Pharmacopeia. 10 In this study, we evaluated the use of a 10 mg omeprazole capsule from a single source Adverse GI effects are frequently reported in dogs after PPI administration, with the most common reported adverse events being vomiting and diarrhea. 4,5,11 Vomiting was limited to 3 episodes in 2 dogs receiving omeprazole.…”

Section: Discussionmentioning

confidence: 99%

“…In other countries such as Cambodia, generic omeprazole formulations have been demonstrated to vary widely because of the use of cheaper coating substitutes and, consequently, premature release of the drug in the stomach 9 . However, it should be noted that in a study evaluating 5 generic omeprazole products in the United States, all 5 products met the in vitro drug dissolution standards established by the United States Pharmacopeia 10 . In this study, we evaluated the use of a 10 mg omeprazole capsule from a single source (TriviumVet) undergoing FDA approval for use in dogs to explore 0.5 to 1.0 mg/kg tailored dosing and to evaluate the efficacy of the product in increasing gastric pH in dogs.…”

Section: Discussionmentioning

confidence: 99%

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A prospective, randomized, masked, placebo‐controlled crossover study for the effect of 10 mg omeprazole capsules on gastric pH in healthy dogs

Gaier

Price

Grubb³

et al. 2021

Veterinary Internal Medicne

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Background: Enteric-coated omeprazole capsules are commonly used as a gastric acid suppressant in dogs. However, the efficacy of this formulation has not been evaluated for clinical use in dogs. Hypothesis/Objectives: To evaluate the efficacy of a 10 mg PO omeprazole capsule (TriviumVet) undergoing FDA approval to increase gastric pH in dogs. We hypothesized that encapsulated omeprazole would significantly increase the gastric pH compared to placebo and reach pH goals extrapolated from people for the treatment of esophagitis and duodenal ulceration. Animals: Six healthy research dogs. Methods: Randomized, blinded, 2-way crossover study. Dogs were PO administered omeprazole at 0.5 to 1.0 mg/kg or placebo (empty gelatin capsules) twice-daily for 5 days. The intragastric pH was recorded on days 2 to 5 of treatment. Mean pH and the mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were compared between and within treatment groups. Results: Dogs treated with omeprazole had a significantly higher MPT ± SD intragastric pH ≥3 (91.2% ± 11.0%), ≥4 (86.9% ± 13.7%) and mean ± SD pH (5.4 ± 0.8) than dogs treated with placebo (19.7% ± 15.5%, 28.3 ± 20.7, and 2.4 ± 1.0, respectively) (P < .001 for all). Conclusions and Clinical Importance: The 10 mg enteric-coated omeprazole capsule PO administered evaluated in this study is an effective gastric acid suppressant in healthy dogs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A prospective, randomized, masked, placebo‐controlled crossover study for the effect of 10 mg omeprazole capsules on gastric pH in healthy dogs

Gaier

Price

Grubb³

et al. 2021

Veterinary Internal Medicne

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“…In accordance to the pharmacopoeia, in-vitro drug release from enteric-coated formulations should be tested in two stages at two different pH which is intended to mimic the pH in the stomach ("gastric phase") and intestinal environment ("intestinal phase") (29). For the testing of delayed-release omeprazole pellets in the "gastric phase", 500-1000ml of 0.1N solution of hydrochloric acid with pH 1.2 as dissolution media and Apparatus I or II at the rotation speed 50-100rpm for 2 h are usually used (1,20,30,31). In accordance with the pharmacopoeia, phosphate buffer solution with a pH of 6.8 should be used during the dissolution test to mimic the intestinal environment (31).…”

Section: Dissolution Test and Acid Resistance Of Commercial Delayed-r...mentioning

confidence: 99%

“…For the testing of delayed-release omeprazole pellets in the "gastric phase", 500-1000ml of 0.1N solution of hydrochloric acid with pH 1.2 as dissolution media and Apparatus I or II at the rotation speed 50-100rpm for 2 h are usually used (1,20,30,31). In accordance with the pharmacopoeia, phosphate buffer solution with a pH of 6.8 should be used during the dissolution test to mimic the intestinal environment (31). Previously it has been shown that the dissolution of omeprazole at pH 6.5 is not reliable and can lead to incorrect conclusions because of the short omeprazole half-life at this pH, while phosphate buffer with pH 7.4 gave reproducible and discriminative results (20).…”

Section: Dissolution Test and Acid Resistance Of Commercial Delayed-r...mentioning

confidence: 99%

Effect of Elevated pH on the Commercial Enteric-Coated Omeprazole Pellets Resistance: Patent Review and Multisource Generics Comparison

et al. 2021

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Omeprazole is a widely used over-the-counter (20 mg) proton pump inhibitor, usually supplied as oral enteric-coated pellets intended to release at pH 5.5 and higher however it is sensitive to acidic pH. The likelihood of elevated gastric pH in practice is very high for patients thus, the aim of this study was to investigate the effect of elevated pH on the performance of commercial omeprazole pellets. Commercial enteric-coated delayed-release pellets were tested with water uptake-weight loss (WU-WL) test at pH range between 1.2 and 4.5 in addition to "gastric" (pH 1.2 or 4.5) and "intestinal" (pH 7.4) phase dissolution tests. The range of physical characteristics of pellets was determined with a single pellet size and sedimentation time measurement, followed by the application of modified Stokes' Law equation. The coefficient of variation of pellet size and density, and volume-density determination coefficient (R 2 ) as descriptors of coating thickness and microstructure variability, degree of ionisation of enteric polymers, aqueous solubility and molecular weight of plasticisers have been found useful to explain commercial delayed-release pellets behaviour during WU-WL and dissolution test.Investigated commercial delayed-release pellets demonstrated pH-dependent WU-WL results."Gastric phase" dissolution testing of pellets at pH 4.5 showed the highest omeprazole degradation (48.1%) for Nosch Labs, intermediate values of dose loss (23.4% and 17.1%) for Teva and UQUIFA delayed-release pellets, respectively. Lab Liconsa pellets have been found as the least susceptible (3.2% of dose loss). Additionally, "gastric phase" dissolution test at pH 4.5 significantly influenced omeprazole release during the "intestinal phase". The risk of inadequate therapy associated with intake of investigated enteric-coated delayed-release pellets at elevated gastric pH has been found as minimal for Lab Liconsa and has increased from UQUIFA and Teva to Nosh Labs pellets.

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“…Interestingly, in contrast to the omeprazole products marketed outside the US which may differ in their enteric coating design characteristics, the omeprazole products approved in the US are similarly designed to the RLD to provide comparable protection against acid degradation through pH 5-5.5 (8). It appears, in this instance, that although this was not considered as a precondition for ANDA approval, the US generic manufactures may have been aware of the critical importance of having within their product design, an enteric coating that provides similar protection as the RLD to ensure therapeutic equivalence.…”

Section: Modified-release Drug Products: Impact Of the Active Ingredimentioning

confidence: 95%

Pharmaceutical Equivalence by Design for Generic Drugs: Modified-Release Products

Raw

Lionberger

2011

Pharm Res

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The Office of Generic Drugs has ensured the high quality of generic products based upon two requirements: pharmaceutical equivalence and bioequivalence to the reference listed drug (RLD). This paradigm has been used with success toward ensuring quality generic drug products that provide the same therapeutic benefit as the RLD. Drug products have increased in design complexity; as a result, approaches to ensure therapeutic equivalence must evolve to provide assurance of quality generic drug products. The Food and Drug Administration quality by design initiative (QbD) provides an enhanced evaluation approach by introducing the concept of a quality target product profile (QTPP). The QTPP introduces, within the context of the current regulatory framework, the quality concept of "pharmaceutical equivalence by design." This article illustrates through several examples how this QbD element in the evaluation of modified-release drug products enhances the current framework to ensure generic drug product equivalence. It achieves this by complementing the traditional paradigm, "equivalence by testing," where product equivalence is based upon inferences from a limited bioequivalence study, to one that also considers whether the drug product was developed to be an equivalent to the RLD, using appropriate quality surrogates that target "pharmaceutical equivalence by design."

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Generic omeprazole delayed-release capsules: in vitro performance evaluations

Abstract: There is no scientific evidence to support the claims that the generic omeprazole delayed-release capsules perform differently from the brand omeprazole product in vitro.

Cited by 12 publications

References 2 publications

A prospective, randomized, masked, placebo‐controlled crossover study for the effect of 10 mg omeprazole capsules on gastric pH in healthy dogs

A prospective, randomized, masked, placebo‐controlled crossover study for the effect of 10 mg omeprazole capsules on gastric pH in healthy dogs

Effect of Elevated pH on the Commercial Enteric-Coated Omeprazole Pellets Resistance: Patent Review and Multisource Generics Comparison

Pharmaceutical Equivalence by Design for Generic Drugs: Modified-Release Products

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