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

Longjian, Geng; Han, Lidong; Lu-Lu, Huang; Wu, Ziheng; Wu, Zhenghong; Qi, Xiaole

doi:10.23937/2469-584x/1510068

Cited by 5 publications

(4 citation statements)

References 36 publications

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“…The US Food and Drug Administration recommends lansoprazole and omeprazole as CYP2C19-sensitive index substrates for clinical drug interaction studies [ 29 ]. However, these drugs increase gastric pH by themselves and this increase in gastric pH likely affects their absorption due to their physicochemical properties, classified as Biopharmaceutical Classification System (BCS) class II [ 30 , 31 ]. Therefore, lansoprazole and omeprazole are considered inappropriate for use in drug metabolism-mediated interaction studies of acid-reducing agents.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of CYP2C19-Mediated Pharmacokinetic Drug Interaction of Tegoprazan, Compared with Vonoprazan or Esomeprazole

Yang

Jang

et al. 2023

Clin Pharmacokinet

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Background and Objective CYP2C19-mediated drug interactions of acid-reducing agents are clinically important given the high possibility of concomitant administration with CYP2C19 substrates. This study aimed to evaluate the effect of tegoprazan on the pharmacokinetics (PK) of a CYP2C19 substrate, proguanil, compared with vonoprazan or esomeprazole. Methods A two-part, randomized, open-label, two-sequence, three-period crossover study was conducted in 16 healthy CYP2C19 extensive metabolizers (eight subjects per part). In each period, a single oral dose of atovaquone/proguanil 250/100 mg was administered alone or co-administered with tegoprazan 50 mg, esomeprazole 40 mg (Part 1 only) or vonoprazan 20 mg (Part 2 only). The plasma and urine concentrations of proguanil and its metabolite, cycloguanil, were measured up to 48 h post-dose. PK parameters were calculated using a non-compartmental method and compared between administered alone and co-administered with tegoprazan, vonoprazan or esomeprazole. Results Co-administration of tegoprazan did not significantly affect the systemic exposure of proguanil and cycloguanil. In contrast, co-administration of vonoprazan or esomeprazole increased proguanil systemic exposure and decreased cycloguanil systemic exposure, and the magnitude of the corresponding change was greater with esomeprazole co-administration than vonoprazan co-administration. Conclusion Tegoprazan, unlike vonoprazan and esomeprazole, exhibited negligible CYP2C19-mediated PK interaction. It suggests that as an alternative to other acid-reducing agents, tegoprazan can be used concomitantly with CYP2C19 substrates in clinical settings. Trial Registration Clinicaltrials.gov identifier: NCT04568772 (Registered on September 29, 2020).

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Section: Discussionmentioning

confidence: 99%

Evaluation of CYP2C19-Mediated Pharmacokinetic Drug Interaction of Tegoprazan, Compared with Vonoprazan or Esomeprazole

Yang

Jang

et al. 2023

Clin Pharmacokinet

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“…Co., Ltd. Yongin-si, Republic of Korea) with a 10 mg dosage of Ila [ 14 , 15 , 16 , 17 , 18 ]. These PPI typically belong to BCS class II, presenting absorption challenges due to low aqueous solubility [ 19 , 20 , 21 , 22 , 23 ]. Additionally, concerns such as the emergence of specific impurities causing color changes during a 30-day storage at room temperature or in solvents, resulting in a content decrease to as low as 84.2%, have been noted [ 17 , 19 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Storage and Stability as Well as the Dissolution Rate of Novel Ilaprazole/Xylitol Cocrystal

Nam,

Lim,

Kim

et al. 2024

Pharmaceutics

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Reflux esophagitis, a treatment for gastric ulcers known as Ilaprazole (Ila), is not stable during storage and handling at room temperature, requiring storage at 5 degrees Celsius. In this study, to address these issues with Ila, coformers rich in oxygen (O) and hydroxyl (OH) groups capable of forming hydrogen bonds with were selected. These coformers included Xylitol (Xyl), Meglumine (Meg), Nicotinic acid (Nic), L-Aspartic acid (Asp), and L-Glutamic acid (Glu). A 1:1 physical mixture of Ila and each coformer was prepared, and the potential for cocrystal formation was predicted using differential scanning calorimetry (DSC) screening. The results indicated the potential for cocrystal formation in the Ila/Xyl physical mixture. Subsequently, Ila and Xyl were mixed in ethyl acetate (EA) in a 1:1 ratio, and after 28 h of slurry, the formation of Ila/Xyl cocrystal was confirmed through solid-state CP/MAS 13C NMR spectrum analysis, showing intermolecular hydrogen bonding and conformational changes. Furthermore, the 1:1 ratio of Ila/Xyl cocrystal was confirmed through solution-state NMR (1H, 13C, and 2D) molecular structure analysis. To assess the stability of Ila/Xyl cocrystal at room temperature, it was stored and compared with Ila at 25 ± 2 °C and relative humidity (RH) of 65 ± 5% over three months. The results showed that the purity of Ila/Xyl cocrystal remained at 99.8% from the initial purity of 99.75% over the three months, while Ila was predicted to decrease from an initial 99.8% purity to 90% after three months. Additionally, at 25 ± 2 °C and RH 65 ± 5%, a specific impurity B in Ila/Xyl cocrystal was observed to be 0.03% over three months, whereas Ila was predicted to increase from an initial 0.032% to 2.28% after three months. To evaluate the dissolution rate of Ila/Xyl cocrystal, a formulation was prepared and compared with Ila at pH 10, with a dosage equivalent to 10 mg of Ila. The results showed that Ila/Xyl cocrystal reached 55% within 15 min and 100% within 45 min, while Ila was predicted to reach 32% at 15 min and 100% only after 60 min. However, overall, the Ila/Xyl cocrystal showed results equivalent to or exceeding the dissolution rate of Ila. Therefore, it is predicted that the Ila/Xyl cocrystal will maximize its effectiveness as a more convenient crystal structure for formulation development, allowing storage and preservation at room temperature without the need for the problematic 5 °C refrigeration during ambient conditions and storage, addressing the issues associated with Ila.

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“…Ilaprazole (Ila) (Figure 1a) is a proton pump inhibitor (PPI) used to treat gastroesophageal reflux disease and peptic ulcers, available in the market under the trade name Noltec with a 10mg dosage of Ila [14][15][16][17][18]. These PPI typically belong to BCS class II, presenting absorption challenges due to low aqueous solubility [19][20][21][22][23]. Additionally, concerns such as the emergence of specific impurities causing color changes during a 30day storage at room temperature or in solvents, resulting in a content decrease to as low as 84.2%, have been noted [17,19,[24][25].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Storage and Stability as Well as the Dissolution Rate of Novel Ilaprazole/Xylitol Cocrystal

Nam,

Lim,

Kim

et al. 2024

Preprint

View full text Add to dashboard Cite

Reflux esophagitis, a treatment for gastric ulcers known as Ilaprazole (Ila), is not stable during storage and handling at room temperature, requiring storage at 5 degrees celsius. In this study, to address these issues with Ila, coformers rich in oxygen (O) and hydroxyl (OH) groups capable of forming hydrogen bonds with were selected. These coformers included Xylitol (Xyl), Meglumine (Meg), Nicotinic acid (Nic), L-Aspartic acid (Asp), and L-Glutamic acid (Glu). A 1:1 physical mixture of Ila and each coformer was prepared, and the potential for cocrystal for-mation was predicted using differential scanning calorimetry (DSC) screening. The results indi-cated the potential for cocrystal formation in the Ila/Xyl physical mixture. Subsequently, Ila and Xyl were mixed in ethyl acetate (EA) in a 1:1 ratio, and after 28 hours of slurry, the formation of Ila/Xyl cocrystal was confirmed through solid-state CP/MAS 13C NMR spectrum analysis, showing intermolecular hydrogen bonding and conformational changes. Furthermore, the 1:1 ratio of Ila/Xyl cocrystal was confirmed through solution-state NMR (1H, 13C, and 2D) molecular structure analysis. To assess the stability of Ila/Xyl cocrystal at room temperature, it was stored and com-pared with Ila at 25±2°C and relative humidity (RH) of 65±5% over three months. The results showed that the purity of Ila/Xyl cocrystal remained at 99.8% from the initial purity of 99.75% over the three months, while Ila was predicted to decrease from an initial 99.8% purity to 90% after three months. Additionally, at 25±2°C and RH 65±5%, a specific impurity B in Ila/Xyl cocrystal was observed to be 0.03% over three months, whereas Ila was predicted to increase from an initial 0.032% to 2.28% after three months. To evaluate the dissolution rate of Ila/Xyl cocrystal, a formulation was prepared and compared with Ila at pH 10, with a dosage equivalent to 10mg of Ila. The results showed that Ila/Xyl cocrystal reached 55% within 15 minutes and 100% within 45 minutes, while Ila was predicted to reach 32% at 15 minutes and 100% only after 60 minutes. However, overall, the Ila/Xyl cocrystal showed results equivalent to or exceeding the dissolution rate of Ila. Therefore, it is predicted that the Ila/Xyl cocrystal will maximize its effectiveness as a more convenient crystal structure for formulation development, allowing storage and preservation at room temperature without the need for the problematic 5°C refrigeration during ambient con-ditions and storage, addressing the issues associated with Ila.

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

Cited by 5 publications

References 36 publications

Evaluation of CYP2C19-Mediated Pharmacokinetic Drug Interaction of Tegoprazan, Compared with Vonoprazan or Esomeprazole

Evaluation of CYP2C19-Mediated Pharmacokinetic Drug Interaction of Tegoprazan, Compared with Vonoprazan or Esomeprazole

Investigation of the Storage and Stability as Well as the Dissolution Rate of Novel Ilaprazole/Xylitol Cocrystal

Investigation of the Storage and Stability as Well as the Dissolution Rate of Novel Ilaprazole/Xylitol Cocrystal

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