| HS Code | 344658 |
| Product Name | Buserelin Acetate Pharma Grade API |
| Active Ingredient | Buserelin Acetate |
| Drug Class | Synthetic nonapeptide Gonadotropin-Releasing Hormone (GnRH) agonist |
| Therapeutic Category | Hormone therapy; used in prostate cancer, endometriosis, uterine fibroids, precocious puberty, and assisted reproduction |
| Cas Number | 68630-75-1 |
| Molecular Formula | C60H86N16O13·C2H4O2 |
| Molecular Weight | 1299.49 g/mol |
| Grade | Pharmaceutical Grade |
| Appearance | White to off-white lyophilized or amorphous powder |
| Assay | 98.0% to 102.0% on dried basis by HPLC |
| Peptide Content | Meets specification for peptide content on anhydrous basis |
| Solubility | Soluble in water and dilute acetic acid; sparingly soluble in methanol; practically insoluble in non-polar organic solvents |
| Route Of Administration | Oral and Injectable |
| Formulation Compatibility | Suitable for tablets, capsules, granules, and injection formulations |
| Storage Conditions | Store at 2–8°C, protected from light, moisture, and heat; avoid repeated freeze-thaw cycles if reconstituted |
| Shelf Life | Typically 24 months when stored under recommended conditions |
| Residual Solvents | Complies with ICH Q3C guidelines |
| Bacterial Endotoxins | Meets injectable-grade endotoxin limits |
| Specific Optical Rotation | Meets established compendial range for Buserelin Acetate |
| Pharmacopoeial Compliance | Suitable for use in pharmaceutical formulations and meets applicable regulatory standards |
As an accredited Buserelin Acetate 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 | Packaged in double polythene-lined aluminum foil bags inside a sealed fiber drum, net weight 25 kg per drum, ensuring stability and safety. |
| Container Loading (20′ FCL) | One 20-foot FCL containing palletized, drummed Buserelin Acetate Pharma Grade API, safely secured for oral and injectable dosage forms. |
| Shipping | Buserelin Acetate Pharma Grade API requires temperature-controlled shipping (typically 2–8°C) to maintain stability and potency. Ship in insulated, sealed containers with desiccants and temperature loggers. Ensure compliance with pharmaceutical regulations, proper hazardous material documentation, and use validated couriers for global delivery of oral and injectable formulations. |
| Storage | Store Buserelin Acetate Pharma Grade API in a tightly sealed, light-resistant container at 2–8°C (refrigerated), protected from moisture and heat. Keep away from direct sunlight and strong oxidative conditions. For tablet, capsule, granule, oral, or injectable formulations, ensure packaging remains intact and dry. Do not freeze unless manufacturer states otherwise. |
| Shelf Life | Shelf life: 24 months from manufacture when stored at controlled room temperature, protected from light and moisture. |
Compounded as a sterile, isotonic aqueous solution at 0.5–1.0 mg/mL buserelin acetate (expressed as the anhydrous acetate salt), the API is dissolved in Water for Injections with 9.0 mg/mL sodium chloride and adjusted to pH 4.5–5.5 using dilute hydrochloric acid or sodium hydroxide. The bulk solution is passed through a 0.22 µm PVDF sterilizing-grade cartridge filter at 2–5 psi differential pressure and filled into 2 mL Type I borosilicate glass vials under nitrogen overlay on an aseptic filling line equipped with a restrictor-barrier isolator. Production-scale records for this format indicate that peptide adsorption to untreated 316L stainless steel can reduce final assay recovery by 3–8% unless the compounding vessel is pre-rinsed with a 0.1% polysorbate 80 solution or siliconized before the batch. The acetate salt is sensitive to photodegradation at the tryptophan residue; amber Type I vials and light-protected secondary packaging are specified for finished vials.
Manufacturing is conducted under FDA 21 CFR 210 and 211 cGMP for finished pharmaceuticals, with aseptic operations following EU GMP Annex 1. Release testing follows USP <1> for injections, USP <71> for sterility, USP <85> for bacterial endotoxins with an acceptance limit below 0.5 EU/mL, and Ph. Eur. 2.6.14 for bacterial endotoxins; elemental impurity documentation is aligned to ICH Q3D for parenteral exposure. Subvisible particulate monitoring follows USP <787> light obscuration particle count; batch rejection occurs when counts exceed compendial thresholds for ≥10 µm and ≥25 µm per container. The downstream production process includes aseptic filling, stoppering, and capping under Grade A unidirectional airflow within a Grade B background, with in-process bioburden monitoring at ≤10 CFU/100 mL before sterile filtration. Terminal finished product types include 0.5 mg/1 mL and 1.0 mg/2 mL single-dose vials intended for subcutaneous administration in GnRH-agonist down-regulation protocols, commonly initiated in the mid-luteal phase of ART cycles. The solution should not be diluted with phosphate-buffered saline at pH above 7.0 because peptide solubility decreases and subvisible aggregates may form over 24 hours at 2–8°C.
Long-acting injectable formulations rely on acid-terminated poly(lactide-co-glycolide) 50:50 with an inherent viscosity of 0.16–0.24 dL/g. Buserelin acetate is loaded at 2–5% w/w of the polymer mass, yielding a polymer-to-peptide ratio between 20:1 and 50:1. The W/O/W double-emulsion process disperses an aqueous peptide solution containing 0.1% w/v poloxamer 188 into a dichloromethane/polymer phase under high-shear mixing at 8,000–15,000 rpm; the primary emulsion is then transferred into a 2% w/v polyvinyl alcohol continuous phase and hardened by solvent evaporation at 35–40°C under reduced pressure. Microspheres are collected through a 125 µm sieve, washed with Water for Injections, and lyophilized to residual moisture below 1.0%. Burst release is controlled by the inner aqueous droplet size and polymer crystallinity; pilot-batch observations show that a primary emulsion particle size D50 above 10 µm increases 24-hour release beyond 15% and triggers failure of in vitro release criteria.
Solvent removal after microsphere hardening is performed in a jacketed 2 L glass reactor with overhead stirring at 150–300 rpm; dichloromethane is removed by gradual pressure reduction to 250 mbar and then 50 mbar. In-process controls include peptide assay of the washed microspheres by reversed-phase HPLC and residual solvent sampling by headspace GC. Encapsulation efficiency below 80% or volumetric mean diameter outside 40–100 µm triggers rework or batch rejection. Compliance for this dosage form includes ICH Q3C residual solvent limits with methylene chloride ≤600 ppm, USP <71> sterility, USP <85> bacterial endotoxins, and USP <711> in vitro release testing using Apparatus 4 flow-through cells at 37°C with phosphate-buffered saline pH 7.4. Terminal product types include 6.3 mg and 9.45 mg buserelin acetate depot powders for injection that are suspended in 1.5–2.0 mL of an aqueous vehicle immediately before intramuscular or subcutaneous administration for 2–3 month androgen suppression in advanced prostate cancer and endometriosis. Storage of the lyophilized microspheres at 2–8°C in sealed vials with desiccant is required to prevent hydrolytic cleavage of the polyester and peptide loss during shelf life.
For hospital sterile compounding and freeze-dried vial presentation, buserelin acetate is lyophilized from an aqueous bulk containing 1.0 mg/mL peptide, 20 mg/mL mannitol, and 0.1 mM acetate buffer at pH 5.0. The solution is filtered through a 0.22 µm sterilizing-grade membrane and filled into 5 mL Type I glass vials at a nominal fill volume of 1.0 mL, corresponding to a 1.0 mg unit dose after reconstitution. The vials are partially stoppered with bromobutyl closure systems and loaded onto pre-cooled freeze-dryer shelves at -40°C. Primary drying is executed at -20°C and 0.1 mbar for 48 hours, followed by secondary drying at 25°C and 0.05 mbar for 6 hours until the product temperature stabilises and the chamber moisture endpoint remains below 0.1% w/w. The finished lyophilisate is backfilled with nitrogen to 500–700 mbar and stoppered under vacuum.
Release testing includes USP <921> Karl Fischer water content with an acceptance limit of ≤1.0%, USP <71> sterility, and Ph. Eur. 2.6.14 bacterial endotoxin testing at <0.5 EU/vial. The 0.5 mg/vial and 1.0 mg/vial lyophilisate formats are reconstituted with 2 mL of 0.9% sodium chloride injection before subcutaneous or intramuscular use. Incompatibility: the freeze-dried powder should not be reconstituted with bacteriostatic water containing benzyl alcohol when used in neonates or infants because of the potential for gasping syndrome; WFI or 0.9% NaCl is specified on the label.
Collapse of the mannitol cake occurs when the primary drying temperature approaches the glass transition temperature of the frozen matrix; production-scale freeze dryers with thermocouple and Pirani gauges are used to determine the endpoint through comparative pressure measurement. Silicone oil-free stoppers are specified because peptide aggregation at the stopper–solution interface can form subvisible particles above 10 µm after reconstitution.
Compliance and release testing matrix for aqueous and lyophilized parenteral formats is summarised below.
| Quality attribute | Reference method | Aqueous solution limit | Lyophilisate limit |
|---|---|---|---|
| Sterility | USP <71>, Ph. Eur. 2.6.1 | No growth | No growth |
| Bacterial endotoxins | USP <85>, Ph. Eur. 2.6.14 | <0.5 EU/mL | <0.5 EU/vial |
| Water content | USP <921> Karl Fischer | Not applicable | ≤1.0% w/w |
| Residual methylene chloride | ICH Q3C headspace GC | ≤600 ppm | ≤600 ppm |
| Elemental impurities | ICH Q3D ICP-MS | Parenteral PDE values | Parenteral PDE values |
| In vitro release for depot microspheres | USP <711> Apparatus 4 | Not applicable | Not applicable |
The oral route for buserelin acetate is not represented by a marketed human product in EU or US formularies; the compounded tablet/capsule/granule formats are therefore confined to pre-clinical pharmacokinetic screening, toxicology batch supply, and formulation feasibility studies. In these studies, the acetate salt is incorporated at 0.05–0.5% w/w of the total fill mass because the active moiety is administered in microgram-range doses and high dilution improves content uniformity. Published data for this specific configuration is limited. Wet granulation with 3–5% w/w hypromellose binder in a top-spray fluid bed at 50–60°C inlet air temperature has been used to produce granules with particle size D50 125–180 µm; the dried granules are filled into size 3 hard gelatin or HPMC capsules or compressed into 6 mm round tablets with a target hardness of 40–70 N. Enteric coating with Eudragit L100-55 targeting dissolution above pH 5.5 is evaluated to limit gastric peptidase exposure.
Compliance documentation for such batches is aligned to ICH M3(R2) for nonclinical bioavailability, FDA 21 CFR 58 for GLP studies, and USP <711> dissolution for method qualification. Finished product types include 0.25–1 mg capsules, 0.5–2 mg tablets, and oral gavage granules prepared at 0.1 mg/kg dose strength. Operational boundary: unprotected oral granules lose detectable peptide content within 15 minutes in simulated gastric fluid at pH 1.2 due to pepsin-mediated degradation; enteric-coated systems are mandatory for any GI delivery study. Direct compression is restricted by the extremely low dose, poor flow of crystalline peptide, and the analytical burden of content uniformity at 0.1% label claim; wet granulation or slugging is therefore used instead of direct compression when a solid oral batch is required.
In multi-dose veterinary applications for cattle, horses, and rabbits, buserelin acetate is formulated as a sterile aqueous solution at 0.004 mg/mL, a concentration that permits accurate intramuscular dosing of 10–20 µg per animal without excessive peptide loss to container surfaces. The manufacturing process uses a 500 L 316L stainless steel compounding vessel with a bottom-mounted magnetic mixer at 200–300 rpm; the peptide is pre-dissolved in successive 5 L aliquots of Water for Injections before transfer to the full batch, and the solution is adjusted to pH 5.0–6.0 with 0.01 M hydrochloric acid. The bulk is filtered through a 0.22 µm polyethersulfone sterilizing-grade filter and filled into 10 mL or 50 mL multi-dose HDPE vials fitted with silicone elastomer stoppers.
Compliance documentation aligns to EU Regulation 2019/6 for veterinary medicinal products, VICH GL18(R2) for residual solvents, and Ph. Eur. 5.1.1 for sterile products; release tests include USP <71> sterility, USP <85> endotoxin, and a preservative effectiveness test according to USP <51> when a preservative system is used. Terminal product types include 10 mL and 50 mL multi-dose vials containing 0.004 mg/mL buserelin acetate for protocols such as induction of ovulation, treatment of ovarian follicular cysts in cattle, and oestrus synchronisation in equine practice. Operational boundary: repeated needle entry into multi-dose vials requires antimicrobial effectiveness testing under USP <51>; the vial rubber closures must be rechecked for reseal integrity after 20 punctures to prevent contamination during herd-scale use. Benzalkonium chloride is avoided in this format because quaternary ammonium preservatives can bind the acetate peptide and reduce assay recovery during stability storage.
Competitive Buserelin Acetate Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please contact us at +8615365186327 or mail to admin@ascent-chem.com.
We will respond to you as soon as possible.
Tel: +8615365186327
Email: admin@ascent-chem.com
Flexible payment, competitive price, premium service - Inquire now!
Buserelin acetate pharma-grade active pharmaceutical ingredient is a synthetic nonapeptide gonadorelin analogue supplied as a white to off-white lyophilized powder for injectable, nasal, and oral solid dosage form development. The peptide sequence contains D-Ser(tBu) at position 6 and ethylamide at the C-terminus, which reduce enzymatic cleavage and increase gonadotropin release compared with native gonadorelin. The acetate salt is identified by CAS 68630-75-1 and is released against a peptide assay of 95.0%–102.0% on an anhydrous, acetic-acid-free basis. Two product models are specified: an injectable-grade model with low bacterial endotoxin and controlled particulate matter, and a solid-dosage-grade model with particle size distribution optimized for roller compaction and Wurster coating. Residual acetic acid is maintained between 4.0% and 8.0%, and water content is routinely not more than 5.0% for injectable-grade powder and not more than 3.0% for solid-dosage powder.
Pharmacologically, buserelin acetate exerts a biphasic pituitary effect. Initial exposure elevates follicle-stimulating hormone and luteinizing hormone; continuous exposure down-regulates gonadorelin receptors and suppresses gonadal steroidogenesis. This mechanism supports use in androgen-sensitive prostate cancer, endometriosis, uterine leiomyoma, central precocious puberty, and assisted reproduction protocols. The injection presentation is typically compounded at 1.0 mg/mL buserelin base in acidified sodium chloride, while a metered nasal spray delivers 0.15 mg per actuation. Unlike small-molecule drug substances, buserelin acetate is not compatible with terminal steam sterilization; aqueous bulk solutions are aseptically filtered through 0.22 µm PVDF or PES membranes and held at 2–8°C before filling.
Published subcutaneous pharmacokinetic data describe an elimination half-life of approximately 80 minutes; intranasal terminal half-life is approximately 1.5 hours, although direct cross-study comparisons are limited by assay and formulation differences. These rapid clearance characteristics require multiple daily dosing for aqueous injection and nasal spray products, which differentiates buserelin from polymer-based depot agonists. The active ingredient is controlled as an acetate salt because the base peptide is hygroscopic and susceptible to aggregation above pH 7.0.
Storage is specified at 2–8°C in sealed polyolefin or Type III glass containers under nitrogen; retest dates are assigned from ICH Q1A stability data. For injectable use, the API package is sealed under nitrogen after vacuum drying to limit oxidation of tryptophan and histidine residues. Identity is confirmed by sequence-specific peptide mapping with trypsin or endoproteinase Glu-C digestion and LC-MS/MS; mass accuracy is controlled within ±0.5 Da of the protonated monoisotopic mass. Infrared spectroscopy according to Ph. Eur. 2.2.24 is used as a batch-to-batch identity fingerprint. Liquid chromatography–mass spectrometry detects sequence variants and acetylation by-products at reporting thresholds below 0.10%.
Release testing for the injectable-grade model follows ICH Q6A and ICH Q3A decision trees. Reverse-phase HPLC on a C18 column with UV detection at 220 nm quantifies peptide content against a bracketed standard; the method is aligned with Ph. Eur. 2.2.29 and USP <621>. Related substances are resolved by sub-2‑µm UPLC with total impurities not more than 2.0% and unspecified impurities not more than 0.5% for a maximum daily dose up to 1 mg; thresholds are adjusted per ICH Q3A dose-dependent criteria. Residual solvents are limited to methanol not more than 3000 ppm, acetonitrile not more than 410 ppm, and triethylamine not more than 320 ppm where used in peptide synthesis.
| Parameter | Test method or standard | Acceptance criterion |
|---|---|---|
| Appearance | Ph. Eur. 2.2.1 / visual | White to off-white lyophilized powder |
| Assay by HPLC | Ph. Eur. 2.2.29 / USP <621> | 95.0%–102.0% on anhydrous, acetic acid-free basis |
| Related substances by UPLC | ICH Q3A decision tree | Total ≤ 2.0%; unspecified ≤ 0.5% |
| Water content | Ph. Eur. 2.5.12 / USP <921> | Injectable grade ≤ 5.0%; solid-dosage grade ≤ 3.0% |
| Acetic acid content | Ion chromatography / GC | 4.0%–8.0% |
| Bacterial endotoxins | Ph. Eur. 2.6.14 / USP <85> | Injectable grade ≤ 0.25 EU/mg |
| Residual solvents | ICH Q3C | Methanol ≤ 3000 ppm; acetonitrile ≤ 410 ppm |
| Elemental impurities | ICH Q3D | PDE-based limits by route and maximum daily dose |
For capsule filling and granule flow control, Hausner ratio is maintained below 1.35 and Carr index below 25%. Tap and bulk densities are determined according to Ph. Eur. 2.9.34; spray-dried solid-dosage material with a median particle size of 10–30 µm typically provides more uniform low-dose capsule filling than milled lyophilized cake. Loss on drying is measured by Ph. Eur. 2.2.32 at 105°C until mass change is less than 0.1%. Particle size distribution is controlled by laser diffraction aligned with ISO 13320, with D90 specified below 75 µm for roller-compacted ribbon feeding. On production capsule lines with dosator nozzles, powders with Hausner ratio above 1.35 often exhibit fill weight variability greater than 4% relative standard deviation and require lubrication with 0.25% magnesium stearate blended for up to 3 minutes; longer blending can increase peptide adsorption to hydrophobic lubricant surfaces.
Sterile injectable manufacturing requires the peptide powder to be reconstituted in water for injection containing sodium chloride and hydrochloric acid to a target pH of 4.0–5.0. The solution is aseptically filtered through 0.22 µm PES capsule filters and filled into Type I glass vials under Grade A unidirectional airflow with Grade B background, as described in EU GMP Annex 1. Terminal autoclaving is avoided because exposure above 60°C accelerates peptide degradation; lyophilisation is the preferred stabilization route. Freeze-drying cycles use primary drying shelf temperatures between -25°C and -10°C and secondary drying below 30°C to keep residual moisture below 0.5% in the cake. Filter integrity after filling is tested by bubble point or diffusion according to ASTM F838-20; PES membrane bubble point in water is typically above 3.0 bar.
Manufacturing bottlenecks on production-scale lyophilizers include heterogeneous ice nucleation, which produces vial-to-vial cake mass variation and moisture spread. Controlled nucleation at -6°C narrows this distribution by aligning ice crystal morphology. If condenser capacity is not maintained below -65°C and chamber pressure below 100 µbar, primary drying can extend beyond 48 hours and increase aggregate content. These controls are critical because subvisible aggregate levels above Ph. Eur. 2.9.19 acceptance criteria can reduce product safety and batch yield. Container closure compatibility studies per ICH Q8 and Ph. Eur. 3.2.1 evaluate extractables from bromobutyl stoppers; silicone oil migration in prefillable syringes can bind peptide and reduce recoverable drug.
Across tablet, capsule, and granule formulation routes, peptide lability in gastric fluid and poor mucosal permeability impose the primary process constraints. Direct compression of buserelin acetate with microcrystalline cellulose and mannitol is acceptable only for non-systemic oral cavity or gastric retention models; systemic oral delivery requires enteric-coated multiparticulates using pH-sensitive methacrylic acid–ethyl acrylate copolymer such as Eudragit L 100-55. Roller compaction is preferred over aqueous wet granulation because residual water above 3.0% promotes peptide aggregation and reduces content uniformity. Granules are prepared with roller compactor gap width of 0.5–1.5 mm and roll pressure between 5 kN/cm and 20 kN/cm; milled granules are classified to 300–800 µm before coating.
Fluid-bed Wurster coating applies the enteric polymer at product temperature 25–30°C and inlet air humidity below 30% RH to avoid premature polymer gelling. Delayed-release dissolution follows USP <711> with an acid stage of 0.1 N hydrochloric acid for 2 hours and a buffer stage at pH 6.8. Published systemic bioavailability data for buserelin oral tablets in humans is limited; the oral solid-dosage model is therefore supplied as a preformulation-grade API for early development, not as a licensed finished oral product. For granules intended for extemporaneous suspension, the powder is subcoated with hydroxypropyl methylcellulose before enteric coating to isolate the peptide from acidic polymer groups. Because buserelin is a substrate for gastrointestinal serine proteases, co-processed formulations may include soybean trypsin inhibitor or aprotinin in an inner phase; however, these excipients must be justified for local and systemic safety.
Structural alteration at position 6 and the C-terminus differentiates buserelin acetate from leuprolide, goserelin, and triptorelin. Buserelin and goserelin share D-Ser(tBu) at position 6; goserelin also contains aza-Gly at the C-terminus, which supports prolonged subdermal implant release. Leuprolide uses D-Leu at position 6 with ethylamide; triptorelin uses D-Trp at position 6 without ethylamide. These substitutions alter receptor binding, metabolic stability, and depot formulation requirements. Buserelin is commonly supplied as aqueous subcutaneous injection and metered nasal spray, while leuprolide and triptorelin are predominantly formulated as polylactic-co-glycolic acid microsphere depots and goserelin as a subdermal implant. This difference reduces the number of residual polymer controls for buserelin, but demands more frequent administration. Published harmonized receptor affinity ranking data across all four agonists in a single assay is limited; the differentiation is therefore based on chemical structure and marketed dosage form rather than numerically ranked potency.
| Parameter | Buserelin acetate | Leuprolide acetate | Goserelin acetate | Triptorelin acetate |
|---|---|---|---|---|
| Position 6 modification | D-Ser(tBu) | D-Leu | D-Ser(tBu) | D-Trp |
| C-terminal modification | Ethylamide | Ethylamide | Aza-Gly amide | Free amide |
| Representative marketed dosage form | Aqueous subcutaneous injection, nasal spray | PLGA depot injection | Subdermal implant | PLGA depot injection |
| Dosing frequency / release | Multiple daily to daily; nasal 2–3 times daily | Monthly to 3-month | 4-week to 12-week | Monthly to 3-month |
During lyophilisation scale-up, batch-to-batch cake mass variation arises from heterogeneous ice nucleation, non-uniform shelf contact, and condenser overload. Vials positioned at the shelf edge can exhibit higher heat flux and lower residual moisture than center vials. This is managed by ramped freezing with controlled nucleation at -6°C, shelf spacing adequate for unidirectional vapor flow, and condenser capacity below -65°C. Chamber pressure is maintained below 100 µbar during primary drying; pressure excursions above 150 µbar are correlated with cake collapse and increased subvisible aggregates. At commercial scale, lyophiliser qualification includes thermal mapping across 12 shelf zones and vial load uniformity testing per ICH Q2(R1) method validation principles.
Routinely, aqueous solutions above pH 7.0 accelerate deamidation and particle formation; the acetate salt should not be compounded with alkaline buffering systems unless pH is re-adjusted to below 6.5. Avoid exposure to strong oxidising agents such as hydrogen peroxide and sodium hypochlorite because tryptophan at position 3 is susceptible to oxidative degradation. The API is incompatible with high-charge-density cationic polymers, which can induce peptide–polyelectrolyte complexation and retard release; oral multiparticulate cores therefore require a hydroxypropyl methylcellulose subcoat. Residual moisture above 5.0% in injectable-grade powder increases aggregation during storage. Desiccated storage at or below 25°C with protection from light is required, and reconstituted peptide solutions should not undergo more than three freeze–thaw cycles.
