As one of the first-line oral iron supplements in clinical practice, Ferrous Gluconate offers core advantages such as high bioavailability of divalent iron (Fe²⁺) and milder gastrointestinal irritation compared to Ferrous Sulfate. However, its efficacy and patient compliance are highly dependent on dosage form design. Different dosage forms adapt to the needs of diverse populations (e.g., children, the elderly, and patients with dysphagia) by adjusting drug release patterns, administration experience, and dosage flexibility. Currently, the mainstream clinical dosage forms include oral solutions, conventional tablets, and sustained-release capsules. These three forms differ significantly in drug release characteristics, indication scenarios, and adverse reaction control, requiring selection based on patients’ physiological traits and medication needs. This article compares them from four aspects—dosage form design principles, core properties, suitable populations, and limitations—to provide references for clinical medication and patient selection.

I. Dosage Form Design Principles: Release Mechanisms Determine Core Differences

The fundamental distinction among the three dosage forms lies in "the rate and site of drug release in the gastrointestinal tract." Their design logic centers on "enhancing iron ion stability, reducing local irritation, and optimizing absorption efficiency," with specific mechanisms as follows:

(I) Oral Solution: Immediate Dissolution and Rapid Release

Ferrous Gluconate oral solutions are mostly clear liquids or suspensions (containing stabilizers such as citric acid and Vitamin C). Their core design is to "maintain Fe²⁺ in the form of soluble ions or micro-suspended particles." After administration, no disintegration is required— the drug dissolves rapidly in the stomach and upper small intestine, and Fe²⁺ is quickly released to the absorption site of the intestinal mucosa (divalent metal transporter 1, DMT1, in the upper small intestine). To prevent Fe²⁺ from being oxidized to poorly absorbable Fe³⁺ during storage and administration, oral solutions usually contain antioxidants (e.g., Vitamin C, sodium sulfite) and chelating agents (e.g., citric acid, which forms stable soluble complexes with Fe²⁺), ensuring that the solution maintains a high concentration of active Fe²⁺ within a short period (e.g., 24 hours) after opening.

(II) Conventional Tablets: Release After Disintegration, Concentrated Absorption

Conventional tablets are compressed using Ferrous Gluconate as the active ingredient, supplemented with excipients such as fillers (e.g., microcrystalline cellulose), disintegrants (e.g., crospovidone), and binders (e.g., hypromellose). Their core design is to "rapidly disintegrate in the stomach and release drug powder." After administration, the tablets enter the stomach and disintegrate into fine powder within 15–30 minutes under the action of gastric acid and disintegrants. Fe²⁺ dissolves from the powder and enters the small intestine for absorption as the stomach empties. Some tablets are coated (e.g., film-coated) primarily to mask the characteristic metallic taste of iron supplements and improve swallowing experience, rather than controlling release rate—drug release still relies on "rapid dissolution after disintegration."

(III) Sustained-Release Capsules: Controlled Release, Slow Absorption

The core design of sustained-release capsules is to "delay Fe²⁺ release through formulation technology to avoid excessively high local concentrations." Common technical approaches include two types: 1) preparing drug powder into "sustained-release pellets" (coated with a controlled-release membrane such as ethyl cellulose) and filling them into capsules; 2) using "matrix-type sustained-release granules" (drug dispersed in a hydrophilic gel matrix such as hypromellose). After administration, the capsule dissolves in the stomach, and the pellets or granules enter the intestine. Fe²⁺ is slowly released through controlled membrane permeation or matrix swelling, maintaining a stable intestinal Fe²⁺ concentration in a "low-concentration, long-duration" state. This avoids the "local high-concentration irritation to the mucosa caused by disintegration of conventional dosage forms" and extends the absorption time (effective absorption window prolonged from 4–6 hours for conventional forms to 8–12 hours).

II. Comparison of Core Properties: From Absorption Efficiency to Administration Experience

The three dosage forms differ significantly in key dimensions such as absorption efficiency, gastrointestinal irritation, administration convenience, and dosage flexibility—directly affecting medication efficacy and patient compliance. The specific comparisons are as follows:

(I) Absorption Efficiency: Oral Solution ＞ Conventional Tablet ＞ Sustained-Release Capsule

Absorption efficiency depends on "the matching degree between Fe²⁺ release rate and intestinal absorption sites." The upper small intestine (duodenum and upper jejunum) is the region with the highest density of DMT1; the faster the drug releases and the higher the concentration at this site, the higher the absorption efficiency.

Oral Solution: No disintegration is required—Fe²⁺ begins to dissolve in the stomach and rapidly reaches the upper small intestine as the stomach empties. It has the shortest time to reach peak absorption (plasma concentration peaks 1–2 hours after administration) and the highest bioavailability. Clinical data shows that under the same dosage, the Fe²⁺ absorption rate of oral solutions is 15%–20% higher than that of conventional tablets.

Conventional Tablet: Disintegration takes 15–30 minutes, so Fe²⁺ reaches the upper small intestine 2–3 hours after administration, with a slightly lower absorption peak. However, it still releases primarily in the upper small intestine (where absorption efficiency is highest), so its bioavailability is second only to oral solutions.

Sustained-Release Capsule: Although it prolongs the residence time of Fe²⁺ in the intestine, the slow release rate means some Fe²⁺ may reach the ileum (where absorption efficiency is lower) with intestinal peristalsis. As a result, its overall bioavailability is 10%–15% lower than that of conventional tablets. However, it excels in stable absorption, avoiding the "large absorption fluctuations" of conventional dosage forms.

(II) Gastrointestinal Irritation: Sustained-Release Capsule ＜ Oral Solution ＜ Conventional Tablet

Gastrointestinal irritation from iron supplements mainly stems from "direct mucosal irritation by high local Fe²⁺ concentrations" and "free radical damage caused by Fe²⁺ oxidation." Dosage forms reduce irritation risk by controlling local concentrations:

Sustained-Release Capsule: Fe²⁺ is slowly released through controlled membranes or matrices, so the local Fe²⁺ concentration in the intestine is always maintained at a low level (approximately 1/3–1/2 that of conventional tablets). It also avoids massive drug accumulation in the stomach, resulting in the lowest incidence of gastrointestinal adverse reactions (e.g., nausea, abdominal distension, constipation). Clinical studies show that the adverse reaction rate of the sustained-release capsule group is 15%–20%, significantly lower than the 35%–40% of the conventional tablet group.

Oral Solution: Although Fe²⁺ releases rapidly, the drug is uniformly dispersed in the gastrointestinal tract in liquid form, with a large mucosal contact area and relatively mild local concentrations. Its adverse reaction rate (approximately 25%–30%) is lower than that of conventional tablets, mostly manifesting as mild nausea, with a low incidence of constipation.

Conventional Tablet: After disintegration, drug powder tends to accumulate locally in the stomach, forming high-concentration Fe²⁺ regions that strongly irritate the gastric mucosa. Especially when taken on an empty stomach, the incidence of constipation and abdominal pain is high, requiring postprandial administration to alleviate irritation.

(III) Administration Convenience: Oral Solution ＞ Sustained-Release Capsule ≈ Conventional Tablet

Administration convenience is directly related to population-specific physiological traits (e.g., swallowing ability, age), with core influencing factors including dosage form morphology, dosage adjustment flexibility, and storage requirements:

Oral Solution: Existing in liquid form, it does not require swallowing solids, making it particularly suitable for children (infants can be fed via dropper), the elderly (with reduced swallowing function), and patients with dysphagia (e.g., post-esophageal cancer surgery). It also allows flexible dosage adjustment—dosage can be precisely controlled according to patient weight (e.g., 3–6 mg/kg elemental iron for children) or therapeutic needs (e.g., 5 mL or 10 mL per dose). Additionally, its taste can be improved by adding sweeteners (e.g., sucrose, steviol glycosides) and flavorings (e.g., orange, strawberry), resulting in significantly higher compliance in children than solid dosage forms.

Sustained-Release Capsule & Conventional Tablet: Both are solid dosage forms that require whole swallowing (sustained-release capsules cannot be opened, as this destroys the controlled-release structure and causes sudden drug release, leading to irritation). They are difficult to administer to patients with weak swallowing ability (e.g., children under 5 years old, stroke patients). Dosage adjustment is limited—most have fixed specifications (e.g., conventional tablets contain 34 mg elemental iron per tablet, sustained-release capsules contain 50 mg elemental iron per capsule) and cannot be split on demand, making them only suitable for adults or older children with matching dosages.

Storage Requirements: After opening, oral solutions need to be refrigerated (2–8℃) and used within a short period (e.g., 7 days), otherwise they are prone to deterioration due to microbial contamination or Fe²⁺ oxidation. Solid dosage forms (tablets, sustained-release capsules) can be stored at room temperature (<25℃) when sealed, with a shelf life of 2–3 years, making them more suitable for long-term medication or home storage.

(IV) Stability: Conventional Tablet ＞ Sustained-Release Capsule ＞ Oral Solution

Stability mainly depends on "Fe²⁺ oxidation rate" and "the ability of the dosage form to resist external factors (e.g., light, moisture, oxygen)":

Conventional Tablet: Most have a film coating to isolate air, light, and moisture. The internal drug powder is mixed with antioxidants (e.g., magnesium stearate), which effectively delays Fe²⁺ oxidation. Under sealed room-temperature storage, the change rate of active ingredient content is <5% (within the shelf life).

Sustained-Release Capsule: The capsule shell (mostly hypromellose shells, more moisture-resistant than gelatin shells) and controlled-release membrane provide certain protection. However, the capsule shell is prone to moisture absorption and softening (when relative humidity >60%), leading to drug leakage, so its stability is slightly lower than that of conventional tablets.

Oral Solution: As a liquid system, Fe²⁺ has a large contact area with air and light. Even with added antioxidants, long-term storage still leads to oxidation (the solution color changes from light yellow to dark brown, indicating Fe²⁺ oxidation to Fe³⁺). Additionally, microbial growth is easy after opening (e.g., bacterial reproduction if not refrigerated), resulting in the poorest stability—strict storage conditions must be followed.

III. Summary of Suitable Populations and Limitations

The design differences of the three dosage forms determine their differentiated indication scenarios. Clinical selection must consider the patient’s age, physiological state, disease needs, and medication compliance, avoiding "one-size-fits-all" use:

(I) Oral Solution: Priority for Special Populations, Emphasizing Dosage Flexibility and Compliance

Suitable Populations: Children under 5 years old, infants, the elderly (with dysphagia), patients with swallowing dysfunction (e.g., cerebral palsy, myasthenia gravis), and populations with poor tolerance or compliance to solid dosage forms (e.g., children refusing tablets).

Limitations: Poor stability—requires refrigeration and short-term use after opening; large single-dose volume (e.g., 15–20 mL per dose), which may cause reflux in some patients (e.g., those with nausea and vomiting); contains sweeteners, so diabetic patients need to choose sugar-free versions (e.g., xylitol instead of sucrose) to avoid blood glucose fluctuations.

(II) Conventional Tablet: Priority for Routine Iron Supplementation in Adults, Balancing Efficacy and Convenience

Suitable Populations: Adults with normal swallowing ability (e.g., women of childbearing age with IDA caused by menorrhagia), older children (e.g., children over 10 years old), and patients requiring long-term medication (e.g., 3–6 months of iron supplementation) with limited storage conditions (e.g., no refrigeration equipment).

Limitations: Obvious gastrointestinal irritation—requires postprandial administration; contraindicated in patients with dysphagia; fixed dosage—cannot be adjusted precisely, making it unsuitable for infants and low-weight children.

(III) Sustained-Release Capsule: Priority for Patients with Gastrointestinal Sensitivity, Emphasizing Low Irritation and Long-Acting Effects

Suitable Populations: Adults with severe gastrointestinal reactions (e.g., severe abdominal pain, constipation) after taking conventional tablets (e.g., patients with peptic ulcers), patients requiring long-term iron supplementation and pursuing stable absorption (e.g., patients with chronic kidney disease complicated by IDA), and patients sensitive to medication frequency (sustained-release capsules are mostly administered once daily, while conventional tablets require three times daily, resulting in higher compliance).

Limitations: Cannot be opened for administration—contraindicated in patients with dysphagia; slightly lower bioavailability—requires appropriate dosage increase (e.g., 102 mg elemental iron per day for conventional tablets vs. 150 mg elemental iron per day for sustained-release capsules); higher price than conventional tablets (controlled-release technology increases production costs), leading to heavier economic burden for long-term medication.

The dosage form innovation of Ferrous Gluconate focuses on "enhancing efficacy, reducing irritation, and adapting to populations." Oral solutions, with core advantages of "high absorption, high flexibility, and high compliance," are the first choice for special populations (children, patients with dysphagia). Conventional tablets, relying on "high stability, low cost, and easy storage," are suitable for routine iron supplementation in adults. Sustained-release capsules, characterized by "low irritation, long-acting effects, and low frequency," are designed specifically for patients with gastrointestinal sensitivity. In clinical selection, the misconception of "one optimal dosage form" must be abandoned—comprehensive evaluation should be conducted from five aspects: patient age, swallowing ability, gastrointestinal tolerance, dosage needs, and storage conditions. For example, oral solutions are preferred for iron supplementation in infants, sustained-release capsules for adults with gastrointestinal sensitivity, and conventional tablets for adults requiring routine iron supplementation and pursuing cost-effectiveness. The ultimate goal is to "match dosage forms to needs and balance efficacy and safety." Future dosage form innovation can further focus on "targeted release" (e.g., enteric-coated sustained-release dosage forms to avoid gastric mucosal irritation) and "combined dosage forms" (e.g., compound oral solutions containing Vitamin C, eliminating the need for additional combined medication), to further improve the convenience and effectiveness of iron supplementation.