Acebutolol hcl Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable
- Product Name: Acebutolol hcl Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable
- Factroy Site: Yudu County, Ganzhou, Jiangxi, China
- Price Inquiry: sales10@sinochem-nanjing.com
- Manufacturer: Ascent Petrochem Holdings Co., Limited
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- Acebutolol hcl Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable is typically used in formulations when particle size distribution and polymorphic purity and residual moisture and processing temperature must be controlled within specific ranges.
| HS Code | 464530 |
| Productname | Acebutolol HCl Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable |
| Chemicalname | N-[3-Acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butanamide hydrochloride |
| Casnumber | 34381-68-5 |
| Molecularformula | C18H28N2O4·HCl |
| Molecularweight | 372.89 g/mol |
| Appearance | White or almost white crystalline powder |
| Assay | 98.0%–102.0% (calculated on dried basis) |
| Purity | ≥98.0% (HPLC) |
| Solubility | Freely soluble in water; soluble in ethanol and methanol; practically insoluble in ether |
| Meltingpoint | 141–144 °C |
| Ph | 4.5–6.5 (1% w/v aqueous solution) |
| Pka | 9.4 |
| Logp | 1.8 |
| Storageconditions | Store at 20–25 °C (68–77 °F); excursions permitted 15–30 °C; protect from light and moisture |
| Container | Tightly closed container |
| Dosageforms | Tablet, capsule, granule, injection |
| Routesofadministration | Oral, injectable |
| Pharmacopoeia | USP, BP, EP |
| Therapeuticcategory | Beta-adrenergic blocker; antiarrhythmic; antihypertensive |
| Grade | Pharma Grade / API |
| Watercontent | ≤0.5% |
| Residueonignition | ≤0.1% |
| Heavymetals | ≤20 ppm |
| Shelflife | 24–36 months when stored properly |
As an accredited Acebutolol 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.
| Packing | Acebutolol HCl Pharma Grade API supplied in double polyethylene-lined fiber drums, 25 kg net, for tablets, capsules, granules, oral and injectable use. |
| Container Loading (20′ FCL) | Container Loading (20′ FCL): Acebutolol HCl Pharma Grade API for oral/injectable tablet, capsule, granule, packed in sealed palletized drums. |
| Shipping | Acebutolol HCl Pharma Grade API is shipped in securely sealed, tamper-evident, moisture-barrier drums or cartons, double-lined with polyethylene bags. Each batch includes COA, MSDS, and labels. Transported under cGMP/GDP at controlled ambient temperature, protected from light, moisture, and contamination, with appropriate customs and safety documentation. |
| Storage | Store Acebutolol HCl Pharma Grade API in a cool, dry, well-ventilated area, away from heat, moisture, direct sunlight, and incompatible materials. Keep containers tightly closed, protected from light, at controlled room temperature 20–25°C (68–77°F), with excursions 15–30°C. Maintain segregation, cGMP hygiene, and contamination control. For oral or injectable use, follow manufacturer’s labeled storage and handling requirements. Protect from physical damage. |
| Shelf Life | Acebutolol HCl API shelf life: typically 24–60 months when stored below 25°C, dry, light-protected, tightly sealed; confirm exact retest/expiry on supplier COA. |
For a 200 mg acebutolol HCl immediate-release tablet, high-shear wet granulation is selected rather than direct compression because direct compression becomes restricted when the API fraction exceeds 45% w/w of the core mass and the unmilled drug substance exhibits Hausner ratios above 1.35. The core tablet mass is held between 360 mg and 420 mg, placing acebutolol HCl at 47.6% to 55.6% w/w; lactose monohydrate is added at 20% to 30% w/w, microcrystalline cellulose PH102 at 15% to 25% w/w, croscarmellose sodium at 2% to 4% w/w split across intra-granular and extra-granular phases, povidone K30 at 1.5% to 3.0% w/w as an aqueous binder, colloidal silicon dioxide at 0.5% to 1.0% w/w, and magnesium stearate at 0.5% to 1.5% w/w added in final blending. Granulation is carried out in a high-shear granulator with impeller tip speed 4.0 m/s to 6.0 m/s and chopper speed 1500 rpm to 3000 rpm; wet mass loss on drying is targeted at 3.0% to 5.0% w/w, followed by fluid-bed drying at inlet air 55 °C to 65 °C and product temperature 35 °C to 40 °C. Dried granules are milled through a 1.0 mm to 1.5 mm screen using a conical mill at 1000 rpm to 1500 rpm, then blended in a bin blender at 12 rpm for 20 min. Tablets are compressed at main compression force 8 kN to 12 kN to hardness 7 kp to 12 kp, with friability not more than 0.8% per Ph. Eur. 2.9.7 and disintegration not more than 15 min per USP <701>. Dissolution testing follows USP <711> using Apparatus II at 50 rpm in 900 mL of 0.1 M hydrochloric acid at 37 °C ± 0.5 °C, with a typical immediate-release acceptance of not less than 80% dissolved at 30 min. Aqueous film coating is applied to a weight gain of 3% to 5% at inlet air 60 °C to 70 °C, bed temperature 38 °C to 42 °C, atomization air 1.5 bar to 2.5 bar, and pan speed 2 rpm to 6 rpm. Regulatory controls include ICH Q3D for elemental impurities, ICH Q3C(R8) for residual solvents, 21 CFR 210/211 current Good Manufacturing Practice, and the relevant acebutolol hydrochloride monograph in Ph. Eur. The terminal finished dosage type is a film-coated immediate-release tablet containing 200 mg or 400 mg acebutolol HCl for oral administration.
| Component | Function | Proportion (% w/w) | Mass per unit (mg) |
|---|---|---|---|
| Acebutolol HCl | Active pharmaceutical ingredient | 47.6–55.6 | 200 |
| Lactose monohydrate | Diluent | 20–30 | 72–126 |
| Microcrystalline cellulose PH102 | Diluent | 15–25 | 54–105 |
| Croscarmellose sodium | Disintegrant | 2–4 | 7.2–16.8 |
| Povidone K30 | Binder | 1.5–3.0 | 5.4–12.6 |
| Colloidal silicon dioxide | Glidant | 0.5–1.0 | 1.8–4.2 |
| Magnesium stearate | Lubricant | 0.5–1.5 | 1.8–6.3 |
| Aqueous film coating | Coating | 3–5 of core weight | 10.8–21.0 |
What Dissolution Specification Applies to High-Dose Acebutolol HCl Capsules?
Encapsulation of acebutolol HCl at 200 mg in a size 0 hard gelatin capsule generally requires roller compaction rather than direct fill because the uncompacted blend segregates when the API fraction exceeds 50% w/w and the excipient fines remain undensified. The dry granulation step uses a roller compactor at roll pressure 40 kN to 70 kN, roll speed 5 rpm to 10 rpm, and roll gap 2 mm to 4 mm; the ribbons are milled through 0.8 mm to 1.25 mm screens to yield granules with bulk density 0.50 g/mL to 0.65 g/mL and final blend uniformity below 3% RSD. The total filled mass ranges from 300 mg to 400 mg, placing acebutolol HCl at 50.0% to 66.7% w/w; crospovidone is added at 2% to 4% w/w, sodium stearyl fumarate at 1% to 2% w/w, and colloidal silicon dioxide at 0.2% to 0.8% w/w. Automatic encapsulation is performed on a dosator or tamping-pin machine at 60,000 capsules/h to 100,000 capsules/h, with fill weight RSD not more than 2% and compaction pressure adjusted to avoid plug deformation. Dissolution is determined according to USP <711> with Apparatus II at 50 rpm in 900 mL of 0.1 M hydrochloric acid or pH 6.8 phosphate buffer at 37 °C ± 0.5 °C; an immediate-release capsule commonly shows not less than 85% released at 30 min, although a regulatory acceptance limit of 75% at 45 min may be adopted depending on the filing. Uniformity of dosage units follows USP <905> with acceptance value not more than 15, and mass variation is controlled within ±5% for hard gelatin capsules. In-process and release testing are anchored to ICH Q3D, ICH Q3C(R8), 21 CFR 210/211, and particle size distribution by laser diffraction per Ph. Eur. 2.9.3 or USP <786>. The terminal finished dosage type is a hard gelatin capsule containing 200 mg or 400 mg acebutolol HCl for oral administration.
Because terminal sterilisation of acebutolol HCl injection may be constrained by container headspace, pH shift, and solution stability data, aseptic processing with a sterilising-grade filter is the default route unless steam sterilisation at 121 °C for 15 min is qualified for the specific ampoule configuration. The API is dissolved in water for injection at 5.0 mg/mL to 12.5 mg/mL expressed as acebutolol base, with sodium chloride added to produce final osmolality of 280 mOsmol/kg to 320 mOsmol/kg; sodium chloride concentration typically ranges from 0.7% w/v to 0.9% w/v depending on the API contribution, and pH is adjusted to 5.0 to 6.5 using dilute hydrochloric acid or sodium hydroxide. The solution is sparged with nitrogen to dissolved oxygen below 2 ppm and filtered through a 0.22 µm PVDF membrane; filter integrity is tested per ASTM F838-20 or Ph. Eur. 5.1.2. Filling into Type I glass ampoules or vials occurs under Grade A laminar flow, with headspace oxygen controlled to less than 2% v/v and container glass evaluated per USP <660>. Particulate matter by light obscuration per USP <788> is controlled to not more than 6000 particles/container at ≥10 µm and not more than 600 particles/container at ≥25 µm; bacterial endotoxins per USP <85> typically use an intravenous limit of not more than 0.5 EU/mL, subject to the marketing authorisation. Leachable testing follows USP <1663> or Ph. Eur. 3.2.2 for elastomeric closures. The terminal finished dosage type is a sterile injection solution in 5 mL or 10 mL Type I glass ampoules or vials for intravenous administration.
Granule Manufacture and the Shift from Aqueous Binder to Dry Binder
Granulation of acebutolol HCl with an aqueous povidone binder is limited by the drug substance’s high water solubility and the resulting potential for solute migration during fluid-bed drying, so dry binder and hydroalcoholic binder systems are sometimes substituted when granule flow and friability become critical. For oral granule production, acebutolol HCl is blended with mannitol or lactose monohydrate, crospovidone, and citric acid at unit proportions that place the API at 16.7% to 25.0% w/w of a 800 mg to 1200 mg granule fill. A binder solution of hypromellose 2910 at 2% to 5% w/w of the dry granulation mass is sprayed in a top-spray fluid-bed granulator at inlet air 60 °C to 70 °C, product temperature 30 °C to 38 °C, spray rate 10 g/min to 30 g/min per 1.0 kg batch, and atomisation pressure 1.5 bar to 2.0 bar. Drying continues to a final loss on drying of not more than 2.5% w/w, followed by screening through 0.5 mm to 1.0 mm and blending with a sweetener-flavour system to offset the API’s bitter taste. Because terminal sachet filling is not the primary pharmacopoeial presentation for acebutolol HCl in major markets, published data for this specific configuration is limited; however, when produced as an oral granule, fill weight uniformity is governed by USP <905> and dissolution by USP <711> if the sachet is a release-tested dosage form. Compliance is supported by ICH Q3D, ICH Q3C(R8), 21 CFR 210/211, and Ph. Eur. 2.9.3 for particle size of the finished granule. The terminal finished dosage type is an oral granule in a unit-dose sachet, with the same granule also used as an intermediate for hard capsule or tablet manufacture.
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- Acebutolol hcl Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable is manufactured under an ISO 9001 quality system and complies with relevant regulatory requirements.
- COA, SDS/MSDS, and related certificates are available upon request. For certificate requests or inquiries, contact: sales10@sinochem-nanjing.com.
The product designation is Acebutolol HCl Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable. The material is the hydrochloride salt of acebutolol, chemically designated as N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butanamide hydrochloride, with CAS number 34381-68-5, molecular formula C18H28N2O4·HCl, and molecular weight 372.89 g/mol. The API is supplied as a white or almost white crystalline powder and is controlled under ICH Q7 for use in finished drug manufacturing. Oral-grade material is intended for compression, encapsulation, and granulation; injectable-grade material is controlled for endotoxins, bioburden, and subvisible particulate matter. Acebutolol HCl is a beta-1 selective adrenergic blocker with intrinsic sympathomimetic activity and membrane-stabilizing activity. It is not intended for direct patient use.
What Compendial and Regulatory Boundaries Define API Release?
Release testing follows the current USP-NF Acebutolol Hydrochloride monograph and the current Ph. Eur. monograph for acebutolol hydrochloride. The assay is determined by validated HPLC or compendial titration and reported on the dried basis with a typical acceptance range of 98.0–102.0%. Related substances are controlled under ICH Q3A(R2) thresholds; unspecified impurities are held at NMT 0.10% and total impurities at NMT 0.5% unless a higher limit is justified by safety data. Residual solvents are limited by ICH Q3C, elemental impurities by ICH Q3D, and potential mutagenic impurities by ICH M7. The finished dosage form remains subject to FDA 21 CFR 210/211, while the API supplier operates under ICH Q7. Table 1 summarizes the release parameter set for oral and injectable supply.
| Parameter | Oral-grade limit and method | Injectable-grade limit and method |
|---|---|---|
| Appearance | White or almost white crystalline powder; visual inspection | White or almost white crystalline powder; visual inspection |
| Assay, dried basis | 98.0–102.0%; HPLC | 98.0–102.0%; HPLC |
| Unspecified impurities | ≤0.10%; ICH Q3A | ≤0.10%; ICH Q3A with additional peak tracking |
| Total impurities | ≤0.5%; ICH Q3A | ≤0.5%; ICH Q3A |
| Residual solvents | ICH Q3C Table 2 limits | ICH Q3C Table 2 limits |
| Elemental impurities | ICH Q3D PDE-based limits; USP <232>/<233> | ICH Q3D PDE-based limits; USP <232>/<233> |
| Water content | ≤0.5%; Karl Fischer titration | ≤0.5%; Karl Fischer titration |
| Microbial enumeration | USP <61>/<62> oral limits | USP <61>/<62> plus sterility USP <71> |
| Bacterial endotoxins | Not routinely specified | USP <85>; limit derived from K/M |
The Hydrochloride Salt Provides Aqueous Solubility but Restricts Direct Compression
Acebutolol HCl is freely soluble in water, and the amine pKa is approximately 9.2, so at physiological pH the molecule is predominantly ionized. This ionization supports dissolution in aqueous granulation and injectable solution processes but contributes to moisture sensitivity and potentially poor powder flow in dry blending. Bulk and tapped density are measured by USP <616>, and derived Hausner ratio and Carr index values determine whether direct compression is feasible. When the Hausner ratio exceeds 1.35, direct compression without a glidant such as colloidal silicon dioxide is not recommended. The product is available as standard crystalline powder and as a micronized grade; micronization by jet milling improves low-dose content uniformity but increases electrostatic charging, requiring processing areas maintained at 40–50% relative humidity.
In a high-shear granulation process, the API is preblended with lactose monohydrate and microcrystalline cellulose before binder addition. Binder systems based on povidone K30 or hypromellose in purified water are used, and fluid-bed drying inlet air temperature is typically held between 40–60°C until loss on drying meets the defined limit. Residual moisture above the specification can cause picking and sticking on tablet tooling. Immediate-release tablets are commonly compressed to hardness of 5–8 kp and tested by USP <701>; uncoated immediate-release tablets should disintegrate within 15 min unless a justified specification is approved. For capsule filling, the powder is granulated to reduce weight variation. Magnesium stearate, when used as a lubricant, is limited to 0.5–1.0% w/w and blended for short durations to avoid delaying dissolution.
When Acebutolol HCl Is Selected Over Atenolol or Metoprolol
Acebutolol HCl differs from several other beta-1 selective blockers by possessing intrinsic sympathomimetic activity and membrane-stabilizing activity in addition to beta-1 receptor blockade. Atenolol and metoprolol do not have clinically relevant intrinsic sympathomimetic activity, and bisoprolol also lacks this property. The pharmacological distinction may produce less pronounced resting bradycardia with acebutolol, but the effect is patient-dependent and does not replace dose titration. Acebutolol is converted in vivo to diacetolol, an active beta-1 selective metabolite. The parent compound has an elimination half-life of 3–4 h, while diacetolol has an elimination half-life of 8–13 h. Atenolol is eliminated largely unchanged by the kidney and has no active metabolite. The FDA-approved oral reference product is available as capsules containing 200 mg or 400 mg of acebutolol HCl. For hypertension, the labeled initial dose is 400 mg once daily or 200 mg twice daily, with a maximum of 1200 mg/day in approved use. For premature ventricular contractions, the labeled starting dose is 200 mg twice daily, with increases to 600–1200 mg/day. Table 2 compares the main beta-1 selective agents.
| Agent | Beta-1 selectivity | Intrinsic sympathomimetic activity | Active metabolite | Parent half-life | Protein binding |
|---|---|---|---|---|---|
| Acebutolol | Yes | Yes | Diacetolol | 3–4 h | 26% |
| Atenolol | Yes | No | None | 6–7 h | <5% |
| Metoprolol | Yes | No | No clinically active metabolite | 3–7 h | 12% |
| Bisoprolol | Yes | No | None | 9–12 h | 30% |
Compared with propranolol, acebutolol is beta-1 selective at lower doses and less lipophilic, which reduces some beta-2-mediated effects but does not eliminate the risk of bronchospasm in susceptible patients. The hydrochloride salt form and aqueous solubility also make acebutolol more suitable for solution-based processing than the free base.
How Does Particle Size Distribution Influence Capsule and Tablet Content Uniformity?
Particle size distribution is measured by laser diffraction according to USP <429>, with D10, D50, and D90 reported. No single distribution is suitable for all dosage forms; the specification is established in the quality agreement based on the intended unit operation. For low-dose tablets, a micronized grade with a D90 near 150 µm or below may be required to achieve content uniformity, while standard crystalline powder may be acceptable for higher-dose wet granulation. In capsule filling, excessive fine particles can cause poor flow and high weight variability, whereas oversized particles can segregate from excipients during transfer. The API particle size specification is therefore one of the primary controls for tablet content uniformity, dissolution rate, and capsule weight variation.
Residual Solvent and Elemental Impurity Risk Control
Residual solvents are limited according to ICH Q3C. Class 1 solvents such as benzene and carbon tetrachloride are avoided unless an exceptional justification exists; Class 2 solvents are controlled to Table 2 limits; Class 3 solvents are limited to 5000 ppm or justified by process capability. Elemental impurities are controlled according to ICH Q3D using the permitted daily exposure approach. For oral and injectable dosage forms, the manufacturer must consider the maximum daily dose of acebutolol HCl and the contribution of excipients, packaging, and manufacturing equipment. Testing is performed by inductively coupled plasma mass spectrometry or optical emission spectroscopy using USP <232>/<233>. Catalyst metals and heavy metal residues from synthesis are reduced to levels consistent with ICH Q3D Option 1 or Option 2A.
Injectable-Grade Specifications and Parenteral Process Limits
Injectable-grade acebutolol HCl is controlled for bacterial endotoxins according to USP <85>, bioburden according to USP <61>/<62>, and sterility according to USP <71> after final processing. The endotoxin limit is calculated as K/M, where K is 5 EU/kg for most parenteral routes and M is the maximum adult dose in mg/kg per hour. Injectable solutions are prepared in water for injection and filtered through a membrane with a nominal pore size of 0.22 µm. If terminal steam sterilization is used, the thermal degradation profile must be generated because published data for this specific injectable configuration are limited. The solution pH is maintained below the amine pKa of approximately 9.2 to preserve ionization and avoid precipitation of the free base. The API should be protected from strong oxidizing agents and excessive heat during processing.
Acebutolol HCl should be stored in tightly closed containers, protected from light, at controlled room temperature. Oral and injectable grades are supplied in HDPE drums with polyethylene liners unless otherwise specified. The retest period and storage statement are defined by ICH Q1A(R2) stability data. The material should not be used in patients with severe bradycardia, second- or third-degree atrioventricular block, cardiogenic shock, or decompensated heart failure, and abrupt withdrawal after prolonged beta-blocker therapy should be avoided because of the risk of angina exacerbation. The API is a manufacturing intermediate and requires further pharmaceutical processing, quality control, and regulatory release before clinical use.
