Bempedoic Acid Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable
- Product Name: Bempedoic Acid 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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- Bempedoic Acid Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable is typically used in formulations when particle size distribution, polymorphic form, and impurity profile and residual solvents, moisture content, and endotoxin levels must be controlled within specific ranges.
| HS Code | 990626 |
| Productname | Bempedoic Acid Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable |
| Apiname | Bempedoic Acid |
| Chemicalname | 8-Hydroxy-2,2,14,14-tetramethylpentadecanedioic acid |
| Casnumber | 738606-46-7 |
| Molecularformula | C19H36O5 |
| Molecularweight | 344.49 g/mol |
| Grade | Pharma Grade / API |
| Appearance | White to off-white crystalline powder |
| Assay | 98.0% to 102.0% |
| Purity | ≥98.0% |
| Watercontent | ≤0.5% |
| Heavymetals | ≤20 ppm |
| Residualsolvents | Controlled as per ICH Q3C |
| Solubility | Practically insoluble in water; soluble in ethanol and DMSO |
| Meltingpoint | 94-96°C |
| Storageconditions | Store at 20-25°C, protected from light and moisture |
| Shelflife | 24 to 36 months |
| Packaging | Double LDPE bag inside HDPE drum |
| Dosageforms | Tablet; Capsule; Granule; Injection |
| Routeofadministration | Oral; Injectable |
| Therapeuticclass | Lipid-lowering agent; ATP citrate lyase inhibitor |
| Qualitystandard | USP/EP/In-house |
| Manufacturinguse | For tablet, capsule, granule, and injection manufacturing |
As an accredited Bempedoic Acid 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 | Bempedoic Acid Pharma Grade API packaged in 25 kg double-lined fiber drums, securely sealed for tablet, capsule, granule, oral, and injectable applications. |
| Container Loading (20′ FCL) | 20′ FCL loaded with palletized Bempedoic Acid Pharma Grade API for tablet/capsule/granule/injection, oral & injectable; securely stowed, sealed, and shipped. |
| Shipping | Bempedoic Acid Pharma Grade API is shipped in sealed, light-resistant, tamper-evident containers under controlled temperature, with desiccants. Handled per cGMP/GDP, it includes CoA, SDS, and compliant labeling. Suitable for oral and injectable formulations, it must be protected from moisture, heat, freezing, and contamination during transport. Store upright. |
| Storage | Store Bempedoic Acid Pharma Grade API in original, tightly sealed containers in a clean, dry, well-ventilated area at controlled room temperature (20–25°C; excursions 15–30°C). Protect from light, moisture, heat, and oxidizing agents. Keep segregated under cGMP status. For injectable-grade material, handle in appropriate cleanroom conditions and maintain container integrity throughout shelf life. Avoid freezing. Follow label and pharmacopeial requirements. |
| Shelf Life | Typically 24–36 months when stored in sealed, light-resistant containers at controlled room temperature; exact expiry varies by manufacturer and dosage form. |
Direct compression of 180 mg bempedoic acid in a single-station research press is rarely predictive of production-scale behavior on rotary machines. On a 20-station Korsch XL 400 with 8–14 kN main compression force and 2.5–4.0 kN precompression, core tablets of 480 mg nominal mass exhibit capping if the API fraction exceeds 45.0% w/w and the blend moisture exceeds 2.0% w/w. A preblend of colloidal silicon dioxide 0.5–1.0% w/w and croscarmellose sodium 3.0–5.0% w/w is passed through a 600 µm mesh before charging to a bin blender at 6–12 rpm for 15–25 min. Magnesium stearate is added at 0.75–1.25% w/w and lubrication is stopped at 5 min; longer lubrication retards release in pH 4.5 acetate buffer under USP <711> Apparatus II at 50 rpm with 900 mL medium. Tablet hardness is held at 80–120 N, friability below 0.8% w/w per USP <1216>, and disintegration below 15 min in 0.1 N HCl. The final form is a film-coated immediate-release tablet, 180 mg, manufactured under FDA 21 CFR 210/211 and ICH Q7 for API quality. Direct compression is economically preferred, but its window is narrow because the needle-like crystal habit of bempedoic acid reduces compactibility at high production speeds.
What Happens When a Dicarboxylic Acid API Is Roller Compacted Below 2.0% Moisture?
Roller compaction is selected when direct compression produces capping or insufficient hardness at batch sizes above 100,000 tablets. Bempedoic acid is dried at 40°C for 4–6 h if incoming moisture exceeds 2.0% w/w; low residual moisture reduces sticking to the rolls when ambient relative humidity exceeds 60%. On a Gerteis Mini-Pactor, a roll gap of 2–3 mm, specific compaction force of 8–12 kN/cm, and roll speed of 3–6 rpm produce ribbon density between 1.1–1.3 g/cm³. The ribbons are milled through a 0.8–1.2 mm screen with rotor speed 40–60 rpm. The resulting granules typically show a D50 of 150–250 µm, a Hausner ratio below 1.25, and a Carr index below 23% when tested per USP <1174>. Tablets compressed from roller-compacted granules use intragranular drug load up to 55–65% w/w of the core weight, with extragranular microcrystalline cellulose 20–30% w/w, crospovidone 3.0–5.0% w/w, and sodium stearyl fumarate 0.75–1.0% w/w as an alternative to magnesium stearate where short lubrication is critical. The final unit is a 180 mg immediate-release tablet or capsule intermediate; this granule route is preferred when a capsule product requires higher bulk density and improved powder flow.
Wet Granulation End-Point Control with Povidone K30 Shifts Disintegration at pH 1.2
Aqueous wet granulation of bempedoic acid requires a defined granulating fluid volume because the dicarboxylic acid has low water solubility and can generate hard, slow-dissolving granules if over-wetted. In a high-shear Gral 10 granulator with impeller at 300 rpm and chopper at 1500 rpm, povidone K30 solution 5% w/w is added at 15–20% w/w of the dry blend; the wet massing endpoint is reached in 2–4 min. The wet mass is passed through a Comil equipped with a 5 mm screen, then dried in a Glatt GPCG 3.1 fluid bed dryer with inlet air at 55–60°C and product temperature maintained at 35–40°C until loss on drying is below 2.0% w/w. Dry milling with an 0.8 mm screen at 2000 rpm yields granules with D50 120–180 µm. Extragranular croscarmellose sodium 3.0–5.0% w/w is split between intragranular and extragranular phases to prevent disintegration times stretching beyond 15 min in 0.1 N HCl. Binder levels above 4.0% w/w dry binder are avoided because the resulting granule tensile strength slows dissolution at pH 1.2. Strong alkali granulating fluids are avoided because bempedoic acid contains two carboxylic acid groups and may form salts with altered dissolution. The finished film-coated tablet contains 180 mg bempedoic acid and is tested for dissolution per USP <711> using multi-media conditions to bracket gastric and intestinal pH variability.
| Parameter | Direct compression | Dry granulation | Wet granulation |
|---|---|---|---|
| API moisture before blending | <2.0% w/w | <2.0% w/w | <2.0% w/w |
| Granule D50 | Not applicable | 150–250 µm | 120–180 µm |
| Hausner ratio | <1.25 | <1.25 | <1.20 |
| Tablet hardness | 80–120 N | 90–130 N | 70–110 N |
| Disintegration in 0.1 N HCl | <15 min | <15 min | <15 min |
| Friability | ≤0.8% w/w | ≤0.8% w/w | ≤0.8% w/w |
Encapsulation of pre-compacted bempedoic acid granules on a dosator-type Bosch GKF 2600 capsule filler is performed at 60,000–100,000 capsules per hour. The granulate for capsule filling is sized to a D90 below 400 µm to prevent bridging in the dosator nozzle, and bulk density is controlled at 0.60–0.75 g/mL to ensure fill weight variation below ±5%. Hard gelatin or hypromellose capsules of size 0 or 00 are filled with a target fill weight of 500–600 mg to deliver 180 mg bempedoic acid. The granulate contains bempedoic acid 30–40% w/w, microcrystalline cellulose 25–35% w/w, lactose monohydrate 15–25% w/w, crospovidone 3.0–5.0% w/w, and sodium stearyl fumarate 0.75–1.25% w/w. In-process controls include disintegration per USP <701> in purified water at 37±2°C and content uniformity per USP <905> with acceptance value not exceeding 15.0. The terminal dosage form is a hard capsule intended for patients who require a non-tablet oral solid; no enteric coating is applied unless a pH-dependent release threshold is separately justified by clinical pharmacokinetic data.
Fixed-Dose Composite Uniformity Requirements for Bempedoic Acid–Ezetimibe Tablets
A 180 mg/10 mg fixed-dose tablet of bempedoic acid and ezetimibe is manufactured by first preparing an ordered mixture because ezetimibe is present at only 5.3% w/w of the bempedoic acid mass and has poor aqueous solubility. Ezetimibe with D90 below 10 µm is geometrically pre-blended with microcrystalline cellulose and colloidal silicon dioxide before being added to the main bulk; mixing in a bin blender proceeds at 12 rpm for 20–30 min with an intensifier bar. Blend uniformity testing follows USP <905> and typically uses 10 sampling points with mean 98–102% of label claim and relative standard deviation below 5.0%. Tableting on a 24-station rotary press at main compression force 10–16 kN and precompression force 3–5 kN yields a 500–550 mg core; the core is film-coated with a non-enteric coating to provide moisture protection. The final tablet must meet dissolution criteria for both actives; bempedoic acid release is evaluated in pH 6.8 phosphate buffer, and ezetimibe release is evaluated with surfactants in the medium because of its low solubility. The fixed-dose composite is used for heterozygous familial hypercholesterolemia and established atherosclerotic cardiovascular disease where dual LDL-cholesterol lowering is indicated.
For patients unable to swallow solid oral dosage forms, a 180 mg sachet formulation based on fluid-bed top-spray granulation is prepared with a binder solution of hypromellose 3.0% w/w. Bempedoic acid is pre-blended with lactose monohydrate and xylitol, then fluidized in a Glatt GPCG 3.1 at inlet air temperature 55–60°C and spray rate 8–12 g/min; granules are dried to moisture below 2.0% w/w. The granulate is milled to a D50 of 120–200 µm and filled into aluminum laminate sachets on a vertical form-fill-seal machine with auger dosing. Each sachet contains 180 mg bempedoic acid plus xanthan gum 0.2–0.5% w/w for dispersion; when emptied into 30 mL of water at 20–25°C, the granules disperse within 60 s with gentle stirring. The suspension pH is checked because bempedoic acid dissolution from the dispersed granules is pH-dependent. The terminal product is a single-dose oral granule sachet intended for once-daily administration after dispersion in water, with content uniformity and moisture controls conducted per USP <905> and USP <921>.
When Sterile Filtration Is Attempted with Bempedoic Acid in Polysorbate-Modified Media
Parenteral administration of bempedoic acid has no approved commercial product, and published data for sterile formulation of the free acid are limited. The free acid has pH-dependent aqueous solubility; a 10 mg/mL solution in phosphate buffer at pH 7.4 cannot be reliably achieved without co-solvents or cyclodextrins. Screening formulations for injectable feasibility typically use co-solvent blends containing PEG 300 or propylene glycol at 10–30% v/v, with polysorbate 20 or 80 at 0.05–0.2% w/v to prevent precipitation upon dilution with normal saline. Sterile filtration through a 0.22 µm PVDF membrane is limited by API precipitation if the formulation pH drops below the pKa of the dicarboxylic acid; therefore, the pH is held at 7.5–8.0 during filtration. Terminal sterilization at 121°C for 15 min has not been fully characterized for bempedoic acid, and published data for this specific configuration is limited, so aseptic processing would be the conservative route. A lyophilized or ready-to-use injection of bempedoic acid would require additional solubility and stability work under ICH Q1A(R2) conditions before any commercial claim. The oral routes remain the only marketed dosage forms for this active pharmaceutical ingredient.
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- Bempedoic Acid 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.
Bempedoic acid pharma grade API, CAS 738606-46-7, molecular formula C19H36O5, molecular weight 344.49 g/mol, is manufactured as a white to off-white crystalline powder for oral solid dosage forms. The chemical entity is 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid, supplied as the free acid rather than a salt, hydrate, or co-crystal in standard pharmaceutical-grade material. The compound is a prodrug activated in the liver by very long-chain acyl-CoA synthetase 1 to bempedoic acid-CoA; this thioester inhibits ATP citrate lyase, reduces hepatic cholesterol synthesis, and increases low-density lipoprotein receptor expression. Approved oral tablet presentations contain 180 mg bempedoic acid once daily; a fixed-dose combination with ezetimibe is also approved in several jurisdictions. No injectable presentation is currently approved by the US Food and Drug Administration or the European Medicines Agency.
Model designations offered by API suppliers typically encode particle-size reduction state—micronized, unmicronized, jet-milled, or granulation-ready—rather than a chemical modification. Because no public USP–NF or Ph. Eur. monograph exists for bempedoic acid, release and stability specifications are derived from ICH Q6A decision trees and registered in the active substance master file or drug master file. Analytical procedures are validated under ICH Q2(R1). Manufacture of the pharma grade is expected to follow ICH Q7 good manufacturing practice for active pharmaceutical ingredients, with regional finished-product requirements such as 21 CFR 210/211 applying after formulation.
The pharma grade profile for tablet and capsule applications is defined less by a single universal assay than by a set of risk-based controls aligned with the formulated dose. For a 180 mg tablet, the API represents a high fraction of the core mass, so lot-to-lot variation in particle size distribution, bulk density, tapped density, and residual water exerts direct leverage on blend uniformity and compaction. Laser diffraction per USP 429 and Ph. Eur. 2.9.31 is used to measure particle size distribution. Powder flow is assessed by Ph. Eur. 2.9.16 or USP 1174; compressibility is often characterized on a compaction simulator to anticipate high-speed rotary press behavior. If the API is supplied as a micronized grade, agglomerate formation during storage can reduce flow and require sieving or dry granulation before compression.
Because the molecule is a dicarboxylic acid, pH-dependent solubility and the potential for salt formation in the gut can affect dissolution. The solid-state form is controlled by X-ray powder diffraction and differential scanning calorimetry; the API should remain free of significant amorphous content unless the vendor and marketing authorization holder specifically designate an amorphous dispersion. Particle-size reduction to a micronized grade increases surface area and dissolution rate but can also increase static charge, reduce bulk density, and create handling challenges during capsule filling and tablet compression. These trade-offs are managed through specification of tapped density, angle of repose, and compressibility index, with methods described in USP 616 and Ph. Eur. 2.9.36.
On high-speed rotary tablet presses, flow and compression defects can originate not from the API itself but from the combination of API grade, filler, disintegrant, and lubricant. For bempedoic acid, the high drug load demands that the API particle size distribution be stable across batches. If the API is too fine, blend segregation may occur; if too coarse, dissolution may slow. Dry granulation via roller compaction is frequently preferred because it avoids exposure to moisture and heat, but it can reduce tablet compactibility if the granule is overcompacted. Manufacture of granules for capsules or oral suspension may include a wet granulation step with a granulating fluid selected after compatibility screening. The granulation end point is monitored by impeller power consumption and torque, while residual moisture is measured by loss on drying or Karl Fischer titration.
Capsule and granule processes impose different constraints than direct tablet compression. Capsule filling requires adequately flowing intermediates; poorly flowing API blends are granulated or roller compacted to control weight variation. Granules for oral sachet or suspension require a particle size distribution that balances rapid dispersion with low segregation. In both cases, the active substance should meet a bioburden limit appropriate to non-sterile oral product; microbial limits are determined under USP 61, USP 62, and harmonized Ph. Eur. chapters. Dissolution testing is a routine release and stability control for oral solid dosage forms. Because no compendial monograph exists, the dissolution medium and apparatus are derived from the approved NDA or scientific advice. A common development approach uses USP apparatus 2 at 50–75 rpm in aqueous surfactant media to maintain sink conditions for a low-solubility compound, but the acceptance limits are stage-based and are not set by the API vendor alone.
What Distinguishes the ATP Citrate Lyase Inhibition Route from Statin-Based Therapy?
Bempedoic acid occupies a regulatory class that is mechanistically separate from HMG-CoA reductase inhibitors. Statins reduce cholesterol synthesis by direct inhibition of HMG-CoA reductase; bempedoic acid inhibits ATP citrate lyase, an enzyme upstream of HMG-CoA reductase. The active CoA thioester is formed in liver via very long-chain acyl-CoA synthetase 1, while skeletal muscle has low expression of this activating enzyme. This difference is described in regulatory summaries as a basis for reduced skeletal muscle myotoxicity relative to statins, but phase 3 trial data also identify gout, tendon rupture, and elevated uric acid as adverse events. Clinical positioning is as add-on to maximally tolerated statin therapy or for patients with statin intolerance. The pharmacological difference does not change the crystal form, but it does affect labeling, combination strategies, and target product profile.
Because bempedoic acid acts upstream of HMG-CoA reductase, its inhibition adds to the LDL-lowering effect of statins; it does not compete with the same binding pocket. Compared with ezetimibe, which inhibits intestinal NPC1L1, bempedoic acid acts on hepatic synthesis. Compared with PCSK9 monoclonal antibodies that require subcutaneous injection, bempedoic acid is orally bioavailable as a small molecule. This route difference explains why oral solid dosage forms dominate its approved use, while injectable formulation remains developmental. The ACLY inhibitor class has no other approved small-molecule members, so published comparative data for the same target is limited.
Bempedoic acid is a dicarboxylic acid with a secondary alcohol group; aqueous solubility is low across the physiological pH range. The oral dosage form therefore benefits from particle size reduction and may require surfactant wetting or surface area control. In granulation, binder selection must be compatible with the carboxylic acid groups. Published data for aqueous granulation of bempedoic acid is limited; therefore, process development commonly compares dry granulation and wet granulation with solvent systems. If wet granulation is used, granule moisture content after drying must be controlled before tablet compression. Drying rates and inlet temperature are evaluated under ICH Q8 design-of-experiment studies, with residual water typically justified by stability data rather than generic defaults.
Specification Architecture Without a Compendial Monograph and ICH Q6A Risk Categorization
In the absence of a pharmacopoeial monograph, a representative release specification is presented in the table below. Acceptance limits are illustrative and must be established under ICH Q6A; each limit is tied to a validated analytical method and batch data. Vendor and marketing authorization holder must agree on the final registered limits.
| Quality Attribute | Analytical Procedure | Representative Release Limit |
|---|---|---|
| Appearance | Visual inspection | White to off-white crystalline powder |
| Identification | Infrared absorption and HPLC retention time | Conforms to reference standard |
| Assay | Stability-indicating HPLC | 98.0%–102.0% w/w on anhydrous basis |
| Any unspecified impurity | Stability-indicating HPLC | ≤0.10% area |
| Total related substances | Stability-indicating HPLC | ≤1.0% area |
| Water content | Karl Fischer titration, USP 921 | ≤0.5% w/w |
| Residue on ignition | Sulfated ash, Ph. Eur. 2.4.14 | ≤0.1% w/w |
| Residual solvents | Headspace gas chromatography, USP 467 | Class 3 solvents per ICH Q3C; Class 2 solvents within permitted daily exposure |
| Elemental impurities | Inductively coupled plasma–mass spectrometry, USP 233 | Permitted daily exposures per ICH Q3D |
| Particle size distribution | Laser diffraction, USP 429 | Micronized oral grade typically D90 ≤30 µm, subject to formulation agreement |
| Bulk and tapped density | USP 616 | Report result for formulation use |
| Polymorphic form | X-ray powder diffraction | Conforms to reference diffractogram |
| Microbial limits | USP 61, USP 62 | TAMC ≤103 CFU/g, TYMC ≤102 CFU/g |
Elemental impurities are not controlled by a legacy heavy metals test; they are risk-assessed per ICH Q3D and measured via inductively coupled plasma–mass spectrometry using USP 233. Residual solvents follow ICH Q3C; if the manufacturing route uses no Class 1 or Class 2 solvents, a test may be omitted with appropriate justification. Nitrosamine risk must be assessed under current regional guidance; for a small-molecule synthetic route, nitrosamine potential is controlled by route review and confirmatory testing when indicated. Specification limits for genotoxic impurities, where present, are derived from the threshold of toxicological concern and justified by batch data.
When Injectable Development Is Considered, Aqueous Solubility and Sterility Interfaces Govern
Bempedoic acid is not approved in an injectable dosage form. A pharma grade API qualified for oral solid dosage cannot be automatically extended to parenteral use. Injectable-grade material must meet bacterial endotoxin limits under USP 85, sterility validation, particulate matter limits under USP 787 and USP 788, and container-closure integrity. The low aqueous solubility of bempedoic acid at neutral pH creates an additional formulation barrier. Candidate parenteral formulations would require solubility enhancement strategies such as pH adjustment, co-solvents, cyclodextrins, or lipid emulsion carriers. Published data for these configurations is limited; no phase 3 injectable product has been established.
Sterility assurance for an injectable route would require the API to be supplied with controlled bioburden and low endotoxin. Endotoxin limits for parenteral products are derived from dose and route; for a theoretical once-daily dose of 180 mg by injection, the limit would follow USP 85 calculations, but no approved product exists. Sterile filtration of a solution requires complete dissolution and filter compatibility; the low aqueous solubility of bempedoic acid at neutral pH complicates this approach. Lyophilization or terminal sterilization would require thermal stability data and moisture level control. Without published phase 3 injectable data, these remain exploratory.
In comparison with statins, ezetimibe, and PCSK9 inhibitors, bempedoic acid API is characterized by an oral small-molecule route, once-daily dosing, and hepatic activation. No cold-chain storage is required; controlled room temperature in double low-density polyethylene bags inside a high-density polyethylene drum with desiccant is typical. Retest intervals are assigned from long-term stability data under ICH Q1A. Fixed-dose combination development with ezetimibe requires a second API-specific particle size specification and binary blend compatibility testing. Packaging and transportation are qualified under controlled room temperature conditions; protection from moisture and light is required to maintain the specified crystal form and impurity profile.
