| HS Code | 533631 |
| Product Name | DL-Carnitine HCL Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable |
| Synonyms | DL-Carnitine Hydrochloride; DL-Carnitine HCl; (RS)-Carnitine Hydrochloride |
| Cas Number | 461-05-2 |
| Molecular Formula | C7H16ClNO3 |
| Molecular Weight | 197.66 g/mol |
| Appearance | White crystalline powder |
| Assay | 98.0% to 102.0% on dried basis |
| Grade | Pharma Grade API |
| Pharmacopoeia Standard | USP / EP / BP / In-house as applicable |
| Solubility | Freely soluble in water; soluble in ethanol; practically insoluble in acetone |
| Ph | 2.5 to 3.5 for 5% aqueous solution |
| Storage Conditions | Store in a tight, light-resistant container at controlled room temperature |
| Dosage Forms | Tablet, capsule, granule, injection |
| Routes Of Administration | Oral and injectable |
| Packaging | 25 kg fiber drum with double polyethylene bags |
| Shelf Life | 24 months when stored properly |
As an accredited dl-carnitine HCL Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
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Direct compression of DL-carnitine hydrochloride at an API mass fraction of 60–75% w/w is used for immediate-release tablet manufacture, but the crystalline racemate’s hygroscopicity and low bulk flow place narrow limits on hopper and die-fill behaviour. Where a tablet is specified to carry 500 mg of DL-carnitine HCl, the calculated API fraction is 76.9% w/w at a 650 mg core, 71.4% w/w at a 700 mg core, and 62.5% w/w at an 800 mg core; the remaining excipient mass is therefore only 150–300 mg per unit. Table 1 provides the mass-balance basis. The formulation is sifted through a 0.5 mm screen, blended in a bin blender at 10–15 rpm for 15–20 min, and lubricated with magnesium stearate for 3–5 min to avoid over-lubrication and dissolution delay. Compression is performed on a high-speed rotary tablet press with a forced feeder; production-scale failure modes include hopper ratholing and rising weight variability when powder-bed moisture exceeds 2.0% w/w. Compression suites are typically maintained at 25–35% RH and 20–25°C. Compliance is assessed under 21 CFR 210/211, ICH Q3D, USP <905> Uniformity of Dosage Units, USP <711> Dissolution, and Ph. Eur. 2.9.5. Terminal product types are uncoated tablets, film-coated tablets, and scored tablets. Published data for direct compression of the exact racemic DL-carnitine HCl grade is limited; material-sparing compaction studies are required before design-space approval.
| Core weight (mg) | Calculated API fraction (% w/w) | Remaining excipient mass (mg) |
|---|---|---|
| 650 | 76.9 | 150 |
| 700 | 71.4 | 200 |
| 800 | 62.5 | 300 |
| 900 | 55.6 | 400 |
Roller compaction is selected when a dry granulation route must eliminate aqueous binder addition and reduce segregation of a high-dose, poorly compressible powder. The dry blend contains DL-carnitine HCl at 60–80% w/w, microcrystalline cellulose or pregelatinised starch at 15–30% w/w, crospovidone at 2–5% w/w, and colloidal silicon dioxide at 0.5–1.0% w/w. The blend is compacted on a roller compactor with ribbed rolls; roll pressure is adjusted to reach ribbon density in the range 1.10–1.40 g/cm³. Ribbons are milled through a 0.8–1.2 mm screen to produce granules with a target D50 of 200–350 µm. The granulation is then blended with extragranular disintegrant and magnesium stearate at 0.5–1.0% w/w before tableting or encapsulation. This route avoids the moisture-induced sticking observed when the hydrochloride salt is subjected to aqueous granulation and preserves fast dissolution because the crystalline API remains partially intact within the granule. Compliance is evaluated under ICH Q1A(R2), USP <711> Dissolution, USP <905> Uniformity of Dosage Units, and USP <701> Disintegration. Terminal product types are immediate-release tablets, dispersible tablets, and hard-shell capsules. The D-isomer present in the racemate is not bioequivalent to L-carnitine; regulatory acceptability must be confirmed in the target jurisdiction before commercial use.
Wet granulation of DL-carnitine HCl is reserved for formulations requiring high-content granules with improved compactibility, but the route demands strict endpoint control because the salt acts as a water sink. The granulation charge contains API at 50–70% w/w, povidone K30 or hypromellose at 2–5% w/w, and microcrystalline cellulose or lactose monohydrate at 20–40% w/w. Purified water is added at 10–25% w/w in a high-shear granulator at impeller speed 150–250 rpm for 3–6 min; the wet mass is passed through a 1.0–2.0 mm screen and dried in a fluid-bed dryer with inlet air at 50–60°C until loss-on-drying reaches 1.0–2.0% w/w. Under-dried granules above 2.0% w/w moisture produce tablet picking and capsule shell softening; overdried granules below 1.0% w/w moisture generate brittle granules with high fines and poor weight uniformity. The dried granules are milled through a 0.8–1.2 mm screen, blended with extragranular disintegrant at 2–5% w/w, and lubricated with sodium stearyl fumarate at 0.5–1.0% w/w to avoid the dissolution delay commonly caused by magnesium stearate in carnitine wet granulations. Compliance includes USP <731> Loss on Drying, ICH Q3D elemental impurities, USP <711>, and Ph. Eur. 2.9.5. Finished product types are granules, coated tablets, and capsules. Published data for the racemic DL-carnitine HCl wet granulation is limited, so pilot-scale moisture studies are required to define the exact water amount.
Dosator and tamping-pin encapsulation lines require granulated DL-carnitine HCl with bulk density between 0.65–0.85 g/mL and maximum moisture below 2.0% w/w; powder slugs or low-density granulations pack unevenly into size 00 or 0 capsules and trigger weight rejection at sustained filling speeds above 60,000 capsules/h. The capsule fill composition is designed to contain 55–75% w/w racemic carnitine HCl, 15–35% w/w microcrystalline cellulose or starch, 2–5% w/w crospovidone, and 0.25–1.0% w/w sodium stearyl fumarate. Encapsulation is performed at 20–25°C and 25–35% RH to prevent moisture transfer to the shell; HPMC capsules require an additional moisture vapour transmission assessment because their shells become brittle at low humidity but soften at higher water activity. In-process controls include mass uniformity, capsule lock length, and disintegration. Regulatory requirements are USP <905>, USP <711>, USP <701>, and 21 CFR 211. Terminal product types are hard gelatin capsules, HPMC capsules, and capsules containing enteric-coated granules. The choice between gelatin and HPMC shell affects filling speed and the permissible finished-product moisture specification.
Single-dose sachet granules dissolve in water before oral administration, so the granule formulation is dominated by water-soluble excipients and a moisture-protective sachet structure. A 1,000 mg DL-carnitine HCl sachet with a total fill weight of 1,500 mg yields a calculated API mass fraction of 66.7% w/w; the remaining mass consists of citric acid at 5–15% w/w, sorbitol or mannitol at 10–30% w/w, flavour and sweetener at 1–5% w/w, and colloidal silicon dioxide at 0.5–1.5% w/w. Granules are prepared by dry blending or by wet granulation with purified water and dried to 1.0–2.0% w/w moisture, then filled on vertical form-fill-seal equipment into a multi-layer laminate sachet with a water vapour transmission rate below 0.5 g/m²/day. Desiccant loading is calculated from the sachet headspace and the marketed pack’s expected climate zone; long-term stability commitments follow ICH Q1A(R2) and photostability evaluation under ICH Q1B. Compliance includes Ph. Eur. 2.9.1 or equivalent powder flow and density tests, USP <671> container performance, and 21 CFR 210/211. Finished product types are oral solution granules, oral suspension granules, and dispersible sachet granules. The hygroscopicity of the hydrochloride salt makes laminate sealant film selection more critical than the granulation process itself.
Parenteral concentrates of DL-carnitine HCl are prepared as aqueous solutions at nominal 200 mg/mL and adjusted to pH 6.0–8.0 with 1 M hydrochloric acid or sodium hydroxide. The solution is filtered through a 0.22 µm sterilising-grade membrane, filled into depyrogenated Type I glass containers, sealed with a nitrogen headspace, and terminally sterilised at 121°C for 15 min with a target F0 ≥ 8. Because the hydrochloride salt dissociates completely, the ideal two-particle osmolarity of the concentrate is approximately 2,024 mOsm/L at 200 mg/mL; Table 2 presents the calculated concentration–osmolarity relationship. Peripheral administration requires dilution into compatible infusion fluid to bring calculated osmolarity below 600 mOsm/L unless a central line is used. In-process controls include bioburden before filtration, filter integrity, pH, density, visual inspection, and subvisible particulate counts under USP <788>. Compliance frameworks are EU GMP Annex 1, USP <1> Injections, USP <85> Bacterial Endotoxins, USP <790> Visible Particulates, and ICH Q3D for elemental impurities. Terminal product types are ampoules, vials, and pre-filled syringes where the container closure system has been validated for terminal sterilisation. The racemic salt must not be extrapolated to L-carnitine parenteral indications unless the national drug authority expressly accepts the D-isomer specification.
| Concentration (mg/mL) | Calculated molarity (mol/L) | Ideal osmolarity (mOsm/L) |
|---|---|---|
| 50 | 0.253 | 506 |
| 100 | 0.506 | 1,012 |
| 200 | 1.012 | 2,024 |
A lyophilised injectable presentation of DL-carnitine HCl is selected where a moisture-sensitive combination product or a specific reconstitution profile is required; the high aqueous solubility of the hydrochloride salt means the drug itself does not require freeze-drying for dissolution. The pre-lyophilisation solution is compounded with API at 80–95% w/w of the dry cake mass and a bulking agent such as mannitol at 5–20% w/w, filled into Type I glass vials, and partially stoppered before freeze-drying. The lyophilisation cycle is product-specific; a conservative cycle includes freezing at −40°C, primary drying at shelf temperature −20°C to −30°C under vacuum, and secondary drying at +20°C until residual moisture is below 1.0% w/w by USP <921>. The lyophilised cake is inspected for collapse, meltback, and particulate matter; container closure integrity is confirmed under USP <1207>. Regulatory compliance includes EU GMP Annex 1, ICH Q1A(R2), ICH Q1B, and USP <788>. Finished product types are sterile lyophilised cakes for reconstitution in vials and dual-chamber cartridge systems. Published data for DL-carnitine HCl lyophilised formulations are limited; cycle parameters must be generated through freeze-drying microscopy and pilot batch characterisation.
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DL-Carnitine hydrochloride (CAS 461-05-2, molecular formula C₇H₁₆ClNO₃, relative molecular mass 197.66 g mol⁻¹) is the racemic hydrochloride salt of 3-hydroxy-4-(trimethylammonio)butanoate. The material is released as a white to almost-white crystalline powder and is freely soluble in water; this solubility profile supports aqueous granulation, capsule dissolution, and the compounding of injectable solutions. The “DL” designation indicates equal proportions of the D- and L-enantiomers, and the racemic solid therefore shows no net optical rotation within polarimetric limits. This property is a primary differentiator from enantiopure L-carnitine hydrochloride, which is specified by a levorotatory specific rotation and is the form most frequently referenced in modern pharmacopoeial monographs.
The product designation used in supply-chain documentation is typically “DL-Carnitine HCl Pharma Grade API,” with the grade defined by the intended route of administration. Oral-grade material is released for tablet, capsule, and granule processing, while injectable-grade material is subject to additional bacterial endotoxin, particulate, and bioburden controls. The synthetic route generally yields the racemate without a chiral resolution step; residual solvents from crystallisation are controlled through ICH Q3C, and elemental impurities are risk-assessed under ICH Q3D. Because the hydrochloride salt is moderately hygroscopic, open handling in areas exceeding 60% relative humidity should be avoided unless the material is preconditioned and the residual water content is re-verified.
| Parameter | Method / standard | Representative acceptance criterion |
|---|---|---|
| Appearance | Visual inspection | White or almost-white crystalline powder |
| Solubility | Ph.Eur. 2.2.7 / USP general notice | Freely soluble in water; slightly soluble in ethanol |
| Assay, anhydrous basis | Potentiometric titration or HPLC | 98.0–102.0% |
| Water content | Karl Fischer, Ph.Eur. 2.5.12 / USP <921> | ≤0.5% for most release specifications |
| Residue on ignition | Ph.Eur. 2.4.14 / USP <281> | ≤0.1% |
| Chloride identification | Ph.Eur. 2.3.1 / USP <191> | White precipitate with silver nitrate; soluble in dilute ammonia |
| Elemental impurities | ICH Q3D / USP <232>, <233> | Class 1 and Class 2A limits as defined by the product risk assessment |
| Residual solvents | ICH Q3C / USP <467> | Class 3 solvents not more than 0.5% each; Class 2 solvents per tabulated limits |
| Microbial enumeration for non-sterile grade | USP <61>, <62> / Ph.Eur. 5.1.4 | TAMC ≤10³ CFU/g, TYMC ≤10² CFU/g, absence of Escherichia coli |
| Bacterial endotoxins for injectable grade | USP <85> / Ph.Eur. 2.6.14 | Derived from K/M calculation; for a 1 g adult dose, typically ≤0.35 EU/mg with K = 5 EU kg⁻¹ |
Powder behaviour is governed by particle-size distribution, crystal habit, residual moisture, and the chloride counterion. DL-carnitine hydrochloride tends to exhibit a crystalline habit that can vary from plate-like to prismatic depending on the final recrystallisation solvent. This habit influences die filling and ejection force on rotary tablet presses. Direct-compression blends typically require the addition of colloidal silicon dioxide at 0.25–1.0% w/w and microcrystalline cellulose to improve flow and compaction. Published quantitative compaction data for this specific racemic hydrochloride as a single component is limited; therefore, compressibility, tablet hardness, and ejection profiles should be generated on the actual blend using an instrumented press.
Moisture uptake remains the primary processing constraint. The hydrochloride form increases aqueous solubility but also increases hygroscopicity relative to some non-chloride salts. If bulk powder is stored at relative humidity above 60%, water absorption can reduce flowability, increase sticking to punch faces, and alter weight uniformity. Pre-conditioning in a humidity-controlled area and verification of water content by Karl Fischer method are required before lubrication. Magnesium stearate is commonly used at 0.25–0.75% w/w, but over-lubrication can delay dissolution because the drug substance is highly water-soluble and the dissolution rate becomes limited by the hydrophobic lubricant film. A low-shear tumble bin blender is usually sufficient; high-shear mixing should be limited to avoid particle attrition and the generation of fines.
Wet granulation is feasible because of the aqueous solubility of the hydrochloride. In a high-shear granulator, the binder solution can be water or a diluted starch paste; the end-point must be controlled to avoid overwetting and solute migration during drying. Fluid-bed drying with inlet air temperature below 60 °C may be used, provided forced-degradation data confirm thermal stability in the intended granulation matrix. The target residual moisture after drying is typically ≤0.5%, measured by Karl Fischer. Roller compaction may be substituted for direct compression when bulk density is too low or flow is poor; the compacted ribbon should be milled to a controlled granule size distribution to reduce segregation in the hopper.
For capsules, DL-carnitine hydrochloride can be filled into hard gelatin or hypromellose shells. Filling machines with dosator or tamping-pin systems may require adjustment because the powder tends to consolidate under compression. Granulation or a roller-compacted intermediate is preferred over a highly aerated direct-compression blend. Capsule dissolution is generally rapid in aqueous media, and finished-product testing is carried out using USP <711> with degassed water at 37 ± 0.5 °C. An immediate-release acceptance criterion of Q = 80% in 30 minutes is often applied, but the final specification is product-specific and must be justified by the marketing authorisation file.
For granule-filled sachets, particle-size distribution must be controlled to prevent segregation during filling. The hydrochloride salt can be dry-blended with a carrier such as mannitol or sorbitol; however, sorbitol mixtures may become tacky at elevated humidity. Foil-laminate sachets offer better moisture protection than polyethylene-only packaging when the product is intended for tropical climates. Content uniformity testing follows USP <905> or Ph.Eur. 2.9.40, and the acceptance value should be computed on the nominal DL-carnitine hydrochloride content, not on the carnitine base equivalent, to avoid arithmetic errors in release.
Injectable dosage forms require a distinct API quality profile. For this route, the material is tested for bacterial endotoxins using USP <85> or Ph.Eur. 2.6.14, and the limit is calculated from the maximum intended adult dose. A formulation containing 200 mg mL⁻¹ carnitine hydrochloride is typical, but the exact concentration must be supported by solubility and osmolality data. The solution is prepared in Water for Injection, and the chloride counterion contributes to osmolality; isotonicity is adjusted with sodium chloride or dextrose only after measuring the freezing-point depression or osmolality of the bulk solution. Terminal sterilisation by moist heat may be evaluated if stability data show no increase in related substances, while aseptic filtration through a 0.22 µm-rated sterilising membrane is used for heat-sensitive formulations. Sub-visible particulate matter in the final container is controlled according to USP <788> or Ph.Eur. 2.9.19.
pH adjustment for injectable solutions is product-specific. Because the hydrochloride salt dissolves to form an acidic solution, careful neutralisation with sodium hydroxide may be required to reach a pH compatible with venous administration and long-term stability. The final pH specification should be derived from forced-degradation and container-closure compatibility studies under ICH Q1A(R2). Glass vials and rubber stoppers are routinely used; extractables and leachables testing should follow the applicable pharmacopoeial and regional guidance. The injectable-grade API should also be tested for visible foreign matter, clarity of solution, and colour of solution where the drug master file includes these tests.
The principal difference between DL-carnitine hydrochloride and L-carnitine hydrochloride is enantiomeric composition, not molecular formula or salt stoichiometry. Both share the formula C₇H₁₆ClNO₃ and relative molecular mass 197.66 g mol⁻¹. The DL form is a racemic mixture; the L form is specified by a negative specific rotation. Substitution of the racemate for the enantiopure L-isomer in a previously approved finished product is not a formulation change that can be made without regulatory assessment, because the D-enantiomer lacks the same biological activity and may affect transporter-mediated disposition. Bioequivalence and safety data generated on L-carnitine hydrochloride cannot be assumed to cover the racemate.
Compared with L-carnitine L-tartrate, the hydrochloride provides a lower molecular weight per active carnitine unit and therefore a higher assay on an equivalent mass basis. L-carnitine L-tartrate contains approximately 68% carnitine base on a weight basis and is often selected for chewable tablets and effervescent formulations because of lower hygroscopicity. Acetyl-L-carnitine hydrochloride is an ester prodrug with different solubility and metabolic fate; its ester bond is susceptible to hydrolysis, and the substance should not be considered interchangeable with DL-carnitine hydrochloride in oral or injectable products. Propionyl-L-carnitine hydrochloride introduces a propionyl ester and requires a separate filing if substituted.
| Attribute | DL-Carnitine HCl | L-Carnitine HCl | L-Carnitine L-tartrate | Acetyl-L-carnitine HCl |
|---|---|---|---|---|
| CAS | 461-05-2 | 6645-46-1 | 36687-82-8 | 5080-50-2 |
| Molecular formula | C₇H₁₆ClNO₃ | C₇H₁₆ClNO₃ | C₁₈H₃₆N₂O₁₂ | C₉H₁₈ClNO₄ |
| Relative molecular mass | 197.66 | 197.66 | 472.49 | 239.70 |
| Optical rotation | Racemic, near zero | Levorotatory, approximately −21.5° to −23.5° | Levorotatory; specification is method-dependent | Levorotatory; specification is method-dependent |
| Moisture sensitivity | Moderate; chloride salt | Moderate; chloride salt | Lower; non-hygroscopic relative to chloride salts | Moderate; chloride salt |
| Primary dosage-form fit | Oral solids and injectable where a racemic source is specified | Oral solids, liquids, and injectables | Chewable, effervescent, and moisture-sensitive solid dosage forms | Oral capsules and tablets; subject to ester hydrolysis |
For tablet, capsule, and granule manufacture, the DL-carnitine hydrochloride grade must be described in the drug master file with the same rigour as other small-molecule APIs. Incoming release testing should include identity by infrared absorption, chloride reaction, assay, water content, residue on ignition, residual solvents, elemental impurities, and microbial limits. For injectable use, the batch record should additionally include endotoxin, bioburden, and particulate-matter data. Processing areas for oral-grade material should be segregated from injectable-grade material if the same equipment is used, and cleaning validation should address carry-over of the chloride salt into non-carnitine products.
Stability studies on the packaged API are conducted under ICH Q1A(R2) conditions; the chloride salt is generally packaged in double polyethylene bags inside a sealed aluminium-lined drum. The container closure should be impermeable to moisture because water uptake can increase cohesiveness and reduce flow. Batch-to-batch variability in particle size is a common processing bottleneck, particularly when a direct-compression blend is transferred from a pilot-scale bin blender to a production-scale rotary press. In such transfers, the compaction profile should be verified at the production compression force, and tablet hardness and dissolution should be checked on multiple sampling points to detect segregation. No additional summary or forward-looking statement is provided beyond this technical description.
