1. Core Challenge: Dilemma in Oral Delivery of Acid-Sensitive Drugs
1. 核心挑战：酸敏感药物口服给药的困境

In modern oral drug delivery, achieving precise targeted release is a core challenge—especially for acid-sensitive active pharmaceutical ingredients (APIs), such as antibody-drug conjugates (ADCs) and small-molecule targeted drugs (e.g., tyrosine kinase inhibitor (TKI) anti-tumor drugs). The acidic environment in the stomach (pH ~1.5-3.5) easily causes hydrolytic degradation of these drugs, leading to reduced bioavailability, fluctuating efficacy, and non-targeted gastrointestinal toxicity. Therefore, developing a delivery system that remains intact in the stomach and enables precise drug release in the intestine is crucial.
在现代口服给药系统中，实现精准靶向释放是一项核心挑战，尤其对于酸敏感的活性药物成分（API），例如抗体药物偶联物（ADC）和小分子靶向药物（如酪氨酸激酶抑制剂（TKI）抗肿瘤药物）而言更是如此。胃部的酸性环境（pH 值约为 1.5-3.5）极易导致这些药物的水解降解，从而降低生物利用度、疗效波动以及产生非靶向胃肠道毒性。因此，开发一种能够在胃中保持完整并在肠道内实现精准药物释放的递送系统至关重要。

2. Key Technology: Why pH-Responsive Enteric-Coated Technology Is Indispensable
2. 关键技术：为什么 pH 响应型肠溶包衣技术不可或缺

This technology cleverly leverages the natural pH gradient of the human gastrointestinal tract:
这项技术巧妙地利用了人体胃肠道的天然 pH 梯度：

· Stomach: Strongly acidic, pH ~1.5–3.5
· 胃：强酸性，pH 值约为 1.5-3.5

· Duodenum/jejunum: pH rises rapidly to ~5.5–7.0
·十二指肠/空肠：pH 值迅速上升至约 5.5-7.0

· Ileum/colon: Near-neutral to weakly alkaline, pH ~7.0–8.0
· 回肠/结肠：近中性至弱碱性，pH 值约为 7.0-8.0

A well-designed enteric coating remains stable in the low-pH gastric environment, acting like a "protective shell"; only when the formulation enters the small intestine (with a higher pH) does the coating dissolve and release the drug—thus achieving targeted delivery and avoiding damage from gastric acid.

3. Core Mechanism: pH-Triggered Dissolution Transition

pH-responsive enteric polymers (e.g., methacrylic acid copolymers, cellulose phthalates) contain ionizable groups, and their dissolution behavior is highly dependent on the environmental pH:

· In the low-pH stomach: Polymers remain in a protonated state and do not dissolve, effectively protecting the internal drug.

· After reaching the specific pH threshold of the small intestine: Polymers undergo deprotonation, dissolve rapidly, and release the drug.

4. Key Applications: Balancing Protection and Efficacy Enhancement

· ADCs and their carriers/hydrolysis-prone small molecules: These molecules often contain acid-labile chemical bonds or functional groups. Enteric-coated capsules minimize gastric degradation, ensuring the drug reaches the absorption site (small intestine) intact—significantly improving systemic bioavailability.

· TKI anti-tumor drugs: Many of these drugs have issues such as a narrow absorption window and pH-dependent solubility. Enteric systems deliver drugs to a more suitable absorption environment (small intestine), optimizing dissolution and absorption processes, improving efficacy consistency, and reducing inter-individual variability.

5. Precise Release: Going Beyond Basic Protection to Achieve Programmed Delivery

Modern enteric technology can achieve more refined control through engineering design:

· Specific intestinal segment release: By selecting polymers with different pH thresholds, selective release in specific segments (e.g., duodenum, jejunum, or ileum) can be achieved.

· Pulsed or phased release: Multi-layer coating designs enable sequential release at different time points or in different intestinal segments.

For drugs with a region-specific absorption window, this precise regulation can yield more optimized pharmacokinetic profiles and lower inter-individual variability.

6. Manufacturing and Formulation Considerations: Ensuring Reproducible Performance

The successful development of enteric formulations requires comprehensive consideration of:

· Polymer selection: Precisely chosen based on the pH of the target release site.

· Coating thickness and uniformity: Balancing gastric protection and timely release in the small intestine.

· Compatibility between APIs and excipients: Avoiding adverse interactions that affect stability or release behavior.

· Consistency in process scaling-up: Using advanced processes (e.g., spray drying, fluidized bed coating) to precisely control coating quality, ensuring batch-to-batch reproducibility and stable release kinetics.

7. Clinical and Regulatory Value: Enhancing Therapeutic Potential

For high-potency drugs (e.g., anti-tumor drugs), enteric systems offer clear clinical advantages:

· Reduce non-targeted exposure, minimizing gastric irritation and related adverse reactions.
· 减少非靶向暴露，最大限度地减少胃刺激和相关不良反应。

· Improve the consistency of bioavailability, ensuring stable and predictable efficacy.
· 提高生物利用度的一致性，确保疗效稳定可预测。

· Potentially reduce dosage or variability, increasing the therapeutic index.
· 有可能降低剂量或变异性，提高治疗指数。

Regulatory authorities increasingly recognize such technologies; the key is to fully demonstrate their design rationality and clinical advantages through reliable in vitro dissolution studies (e.g., using USP dissolution apparatus to simulate gastrointestinal pH transitions) and in vivo pharmacokinetic comparison data.

Conclusion

· Achieving efficient and stable oral delivery of acid-sensitive drugs remains a key R&D challenge.
· 实现酸敏感药物的高效稳定口服递送仍然是研发领域的一项关键挑战。

· pH-responsive enteric-coated capsules provide a proven robust platform: they effectively protect drugs from gastric acid damage and ensure targeted release at the optimal absorption site in the small intestine.
· pH 响应型肠溶胶囊提供了一个经过验证的强大平台：它们能有效保护药物免受胃酸损害，并确保在小肠的最佳吸收部位进行靶向释放。

· For high-end formulations (e.g., ADCs, TKIs), this translates to higher stability, more predictable efficacy, and stronger overall therapeutic value.
· 对于高端制剂（例如 ADC、TKI），这意味着更高的稳定性、更可预测的疗效和更强的整体治疗价值。

If you are developing acid-sensitive drugs and wish to explore how customized enteric solutions can reduce development risks and improve product performance, we welcome discussions at any time.