Erroneous formulation of delayed-release omeprazole capsules: alert for importing countries

Abstract

BackgroundPoor drug quality is a matter of serious concern, especially in countries where drug regulation and law enforcement are constrained by limited resources. This study was carried out to investigate the cause of quality failure of omeprazole in Cambodia in 2010 and Myanmar in 2014.MethodsWe conducted pharmacopoeial quantity, content uniformity and dissolution tests of 156 samples of omeprazole capsules collected in Cambodia in 2010 and Myanmar in 2014. High failure rates were found, especially in dissolution testing, and detailed investigation of several unacceptable samples was carried out by means of in-vitro dissolution profiling, scanning electron microscopy (SEM) and X-ray computed tomography (X-ray CT) to identify the cause of failure.ResultsDissolution profiling with and without the acid stage showed that acid caused premature omeprazole release, indicating that the enteric coating of the omeprazole granules was ineffective. SEM examination of two failed samples revealed cracked and broken granules mixed with apparently intact omeprazole granules in the capsule. X-ray CT examination indicated that some granules of failed samples completely lacked enteric coating, and others had incomplete and non-uniform enteric coating or malformation.ConclusionsOmeprazole capsules collected in Myanmar and Cambodia showed high failure rates in pharmacopoeial tests, especially dissolution tests. Some samples were found to have ineffective or absent enteric coating of the granules, resulting in premature dissolution and degradation in acidic conditions. This is a potentially serious public health issue that needs to be addressed by regulatory authorities in Cambodia and Myanmar, possibly through a collaborative initiative with manufacturers.

Quality of omeprazole purchased via the Internet and personally imported into Japan: comparison with products sampled in other Asian countries

“…In Cambodia 2010, a study conducted by Yoshida et al [14] found serious quality deficiencies, especially in the dissolution test, in omeprazole samples from some manufacturers. Similar results were reported from Myanmar in 2014 by Rahman et al [15]. Interestingly, manufacturers of those poor-quality products had also produced some of the samples obtained in our current study.…”

“…Similar results were reported from Myanmar in 2014 by Rahman et al . . Interestingly, manufacturers of those poor‐quality products had also produced some of the samples obtained in our current study.…”

Substandard and Falsified Medicines in Myanmar

“…In the DS assessment of MF, 1 MF-IR sample out of 49 samples (2.0%) and 9 MF-ER samples out of 13 samples (69.2%) were pending. All the medicines contained an acceptable amount of active ingredient, so the tablets could harden and change in terms of other properties, even though the content may not be lost due, for example, to heat [21,22], since extended release tablets and sustained-release tablets require special technology that may not be readily available to manufacturers in developing countries [23]. Quality-test-failing MF-ER samples were manufactured by one manufacturer out of four.…”

High Anti-Acid Omeprazole Lightweight Capsule for Gastro-Enteric System Acid-Related Disorders Treatment

“…It is widely used for the treatment of gastric and duodenal diseases [16,17], and it also has a good therapeutic effect on most ARDs [11]. OMZ is very poorly soluble [18], but it has high permeability and is highly absorbable (> 90%) in the intestinal tract. It belongs to the biopharmaceutics classification system (BCS) class II [19] and the dissolution rate is a key factor for that ensures a better release.…”

“…The appearance of the capsules is shown in Figure 4a. The capsules we developed were prepared by mixing and filling 170 mg of OMZ-CD, 250 mg of NaHCO 3, and 400 uble [18]; the saturation solubility of OMZ in water and PBS (pH 6.8) were 75.38 ± 1.52 μg/mL and 80.26 ± 1.50 μg/mL (see Figure 2a). In an attempt to minimize these drawbacks, the aim of this work was to evaluate the capability of OMZ for the oral delivery of drug when associated to CD.…”