Propofol Medium and Long Chain Lipid Injectable Emulsion Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable
- Product Name: Propofol Medium and Long Chain Lipid Injectable Emulsion 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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- Propofol Medium and Long Chain Lipid Injectable Emulsion Pharma Grade API for Tablet / Capsule / Granule / Injection, Oral & Injectable is typically used in formulations when lipid-phase ratio, droplet size distribution, and pH and temperature, oxygen exposure, and shear stress must be controlled within specific ranges.
| HS Code | 902834 |
| Product Name | Propofol Medium and Long Chain Lipid Injectable Emulsion Pharma Grade API |
| Active Pharmaceutical Ingredient | Propofol |
| Api Grade | Pharma Grade |
| Chemical Name | 2,6-Diisopropylphenol |
| Iupac Name | 2,6-bis(propan-2-yl)phenol |
| Cas Number | 2078-54-8 |
| Molecular Formula | C12H18O |
| Molecular Weight | 178.27 g/mol |
| Atc Code | N01AX10 |
| Dosage Forms | Tablet, Capsule, Granule, Injection, Oral, Injectable |
| Route Of Administration | Oral and Injectable |
| Appearance | White to off-white sterile lipid emulsion |
| Emulsion Type | Medium and long chain triglyceride lipid emulsion |
| Lipid Composition | Medium-chain triglycerides and long-chain triglycerides |
| Propofol Concentration | Typically 10 mg/mL (1%) |
| Ph | 6.0 to 8.5 |
| Osmolality | Approximately 300 to 310 mOsm/kg |
| Mean Particle Size | Typically less than 500 nm |
| Sterility | Sterile |
| Pyrogenicity | Non-pyrogenic |
| Preservative | Preservative-free or contains antimicrobial preservative depending on formulation |
| Shelf Life | Typically 24 to 36 months when stored as directed |
| Packaging | Glass vial, plastic vial, ampoule, or prefilled syringe |
| Solubility | Practically insoluble in water; formulated as lipid emulsion |
| Manufacturer | Various pharmaceutical manufacturers |
As an accredited Propofol Medium and Long Chain Lipid Injectable Emulsion 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 | Sterile 10 mL clear glass vials, sealed with rubber stoppers and aluminum crimp caps, supplied 50 vials per carton. |
| Container Loading (20′ FCL) | 20′ FCL container loaded with palletized pharma-grade Propofol medium- and long-chain lipid injectable emulsion; temperature-controlled, sealed, and secured for export. |
| Shipping | Propofol Medium and Long Chain Lipid Injectable Emulsion Pharma Grade API ships in sterile, sealed, light-resistant containers under temperature-controlled conditions, typically 15–25°C or 2–8°C per specification. Do not freeze. Use insulated, absorbent, upright packaging with validated carriers. Avoid excessive heat, light, and agitation; maintain documentation and GDP compliance. |
| Storage | Store in a cool, dry, well-ventilated area away from heat, ignition sources, and incompatible materials. Keep containers tightly closed, protected from light, and preferably under inert gas. For the lipid emulsion, maintain the supplier’s recommended temperature—typically 2–8°C or 15–25°C—do not freeze. Use aseptic handling. Rotate stock; inspect for separation or particulates. Follow local regulations. |
| Shelf Life | Typically 18–24 months when stored unopened, protected from light, at controlled room temperature; confirm exact expiry on the COA. |
Terminal steam sterilisation of a 10 mg/mL propofol medium-chain triglyceride/long-chain triglyceride injectable emulsion changes the globule size distribution before the first visual inspection of the vial is performed. In a formulation where propofol is dissolved in a 10% w/v mixed-oil phase composed of soybean oil 50 mg/mL and medium-chain triglycerides 50 mg/mL, the interfacial film formed by egg lecithin 12 mg/mL is the primary boundary against droplet coalescence during 121 °C terminal sterilisation. Production-scale batch records from 500 L stainless steel vessels with nitrogen overlay show that the pre-emulsion temperature is held between 50 °C and 60 °C before transfer to a high-pressure homogenizer; increasing the oil-phase temperature above 65 °C before rotor-stator mixing accelerates oxidative free fatty acid release and reduces the zeta potential contribution from lecithin. The pre-emulsion is therefore passed through an inline rotor-stator device at 800–1,200 bar in 5–7 recirculation cycles, with the heat exchanger set to keep the post-homogenisation temperature below 45 °C. After pH adjustment to 7.0–8.5 with sodium hydroxide, the bulk emulsion is filled into glass vials under nitrogen and terminally sterilised in a counter-pressure autoclave with an F0 of at least 15 min. The finished dose form for central operating theatres is a sterile white oil-in-water injectable emulsion in 20 mL, 50 mL, and 100 mL glass vials or 50 mL ready-to-administer syringes. Release testing for this application requires USP <729> Method I mean droplet diameter below 500 nm, Method II large-diameter tail PFAT5 below 0.05%, USP <788> particulate matter limits for small-volume injections, and USP <85> bacterial endotoxin limits established for intravenous administration. The ICH Q1A(R2) stability programme for the same terminal presentation typically includes stress conditions at 25 °C/60% RH, 2–8 °C, and elevated-temperature excursions because phase separation is a physical instability that cannot be detected by assay alone.
| Parameter | Typical operating value | Acceptance boundary | Reference method or equipment |
|---|---|---|---|
| Mean droplet diameter | 180–350 nm | ≤500 nm | USP <729> Method I |
| Large-droplet tail PFAT5 | 0.01–0.04% | ≤0.05% | USP <729> Method II |
| pH | 7.0–8.5 | 6.0–8.5 | Ph. Eur 2.2.3 / USP <791> |
| Sub-visible particulates | Pass | ≥10 µm: ≤6,000 per container; ≥25 µm: ≤600 per container | USP <788> |
| Homogenisation pressure | 800–1,200 bar | Not exceed 1,500 bar; chamber wear raises D50 | High-pressure homogenizer with diamond interaction chamber |
| Terminal sterilisation F0 | ≥15 min | Not less than validated F0; overpressure maintained | Counter-pressure steam steriliser |
What Happens to Droplet Size Stability When a Sedation Emulsion Moves From Glass Ampoules to Ready-to-Use Syringes?
Moving a propofol MCT/LCT emulsion into sterile ready-to-use syringes for intensive care sedation introduces a second packaging surface. Silicone oil applied to the glass barrel can migrate into the oil phase and enlarge the large-droplet population measured by PFAT5 after 6 h of contact at 25 °C. The processing route for this presentation uses the same 10 mg/mL propofol load dissolved in a 1:1 soybean oil/MCT lipid phase and the same 12 mg/mL egg lecithin interfacial film. The critical process difference is that filling is performed under Grade A with terminal sterilisation of the pre-filled syringe in a counter-pressure autoclave; if the syringe plunger is inserted too deeply before sterilisation, the expandable stopper contact surface compresses the emulsion meniscus and can generate a measurable PFAT5 shift, but published data for this specific plunger insertion configuration is limited. Process validation is therefore required to set the insertion depth against post-autoclave USP <729> Method II results. For intensive care sedation, the terminal presentation is a 50 mL or 60 mL ready-to-administer syringe connected to a syringe driver; compliance with ISO 11040-8 for pre-filled syringes, EU GMP Annex 1, and USP <797> for the hospital preparation environment defines the point of administration. The production scale is smaller than hospital bulk vials because the fill weight tolerance is tighter at ±1.0% and the post-autoclave particle count is evaluated by USP <788> after syringe plunger actuation simulation. The formulation addition ratio remains propofol 10 mg/mL, soybean oil 50 mg/mL, medium-chain triglycerides 50 mg/mL, egg lecithin 12 mg/mL, glycerol 22.5 mg/mL, sodium oleate 0.3 mg/mL, WFI q.s. to 1 mL.
Outside the operating theatre, the same 10 mg/mL propofol MCT/LCT injectable emulsion is used for procedural sedation in endoscopy suites and cardiac catheterisation laboratories where bolus dosing is delivered through low-dead-volume cannulae and the primary risk is not dose calculation but microbial ingress from repeated vial puncture. The formulation addition ratio does not change from the central operating theatre presentation: propofol 10 mg/mL, soybean oil 50 mg/mL, medium-chain triglycerides 50 mg/mL, egg lecithin 12 mg/mL, glycerol 22.5 mg/mL, sodium oleate 0.3 mg/mL, WFI q.s. to 1 mL. The downstream production process is aseptic filling of 20 mL Type I borosilicate glass vials under a restricted access barrier system, nitrogen flushing, stoppering, and terminal steam sterilisation at 121 °C with F0 ≥ 15 min. Because the emulsion contains no antimicrobial preservative, the vial is strictly single-use; once opened, the residual volume is discarded within 6 h according to infection control standards. The terminal finished presentation is a 20 mL single-dose injectable emulsion for intravenous bolus administration in non-operating room procedural sedation. Compliance is governed by 21 CFR 210/211 current good manufacturing practice, USP <729>, USP <788>, USP <85>, and the Ph. Eur. parenteral inspection requirements.
Veterinary Anaesthesia Emulsion Reprocessing Risk in Multi-Dose Handling Environments
Companion animal anaesthesia in veterinary clinics is a separate downstream sector because the same 10 mg/mL propofol MCT/LCT emulsion is administered to catheterised dogs and cats at induction doses that vary by premedication, age, and species; published veterinary formularies report dog induction ranges near 6–8 mg/kg and cat induction ranges near 4–6 mg/kg when premedication is used, but the manufacturer submission controls the authorised label range. The formulation addition ratio remains propofol 10 mg/mL, soybean oil 50 mg/mL, medium-chain triglycerides 50 mg/mL, egg lecithin 12 mg/mL, glycerol 22.5 mg/mL, sodium oleate 0.3 mg/mL, WFI q.s. to 1 mL. The downstream production process uses the same aseptic 20 mL single-use vial line with terminal steam sterilisation; no multi-dose packaging is validated because the absence of an antimicrobial preservative creates a 6 h post-puncture microbial growth boundary. Regulatory compliance for this downstream sector is set by VICH GL3R for stability, 21 CFR 210/211 for manufacture, and the relevant veterinary product registration requirements; the agent is not assigned a maximum residue limit for food-producing species in the European Union, so the terminal presentation is restricted to companion animal single-dose intravenous injection. Published data for MCT/LCT propofol use in large-animal field anaesthesia is limited, and the emulsion is not recommended for unhygienic multi-dose withdrawal from non-sterile farm environments.
Aseptic Fill-Finish of Generic MCT/LCT Propofol Requires Matched Globule Distribution Before Bioequivalence Lot Release
A generic propofol MCT/LCT emulsion submitted through an abbreviated new drug application is not released solely on assay and sterility. The FDA product-specific guidance for propofol injection recommends in vitro bioequivalence testing that includes globule size distribution, PFAT5 large-droplet population, and distribution shape, because variations in homogenisation pressure and lipid phase ratio change the droplet surface area available for pharmacodynamic onset after intravenous injection. The formulation addition ratio in this downstream sector is set to match the reference listed drug: propofol 10 mg/mL, soybean oil 50 mg/mL, medium-chain triglycerides 50 mg/mL, egg lecithin 12 mg/mL, glycerol 22.5 mg/mL, sodium oleate 0.3 mg/mL, WFI q.s. to 1 mL. The production process begins with propeller mixing of the oil phase under vacuum at 50–60 °C, followed by high-shear pre-mixing, high-pressure homogenisation at 800–1,200 bar, and terminal steam sterilisation at 121 °C. Comparative release data from the multi-pass homogeniser are generated using a laser diffraction system capable of detecting the 0.02–1000 µm range; the acceptance criterion is USP <729> Method I mean droplet diameter below 500 nm and Method II PFAT5 below 0.05%. The terminal presentation is a generic 10 mg/mL propofol injectable emulsion in 20 mL and 50 mL glass vials intended for ANDA submission and commercial distribution. Degradation products are monitored under ICH Q3B(R2), with oxidative impurities controlled by nitrogen sparging and headspace oxygen below 2.0% before sealing.
When Clinical Trial Supplies Move From Campaign Production to Individual Kit Labelling
When clinical trial material is produced from the same 10 mg/mL propofol MCT/LCT emulsion bulk, the regulatory emphasis shifts from commercial release to positive blinding and kit-level integrity under EU GMP Annex 13 and 21 CFR 210/211. The formulation addition ratio is not altered: propofol 10 mg/mL, soybean oil 50 mg/mL, medium-chain triglycerides 50 mg/mL, egg lecithin 12 mg/mL, glycerol 22.5 mg/mL, sodium oleate 0.3 mg/mL, WFI q.s. to 1 mL. The downstream process is a campaign split from a 100–200 L bulk batch into smaller nested vials; small-batch filling may use a single-pass homogeniser with a heat exchanger and a Grade A isolator to keep line speed low enough for blinded label reconciliation. Terminal presentations include randomised clinical trial kits for bioequivalence, paediatric, renal impairment, and hepatic impairment cohorts, supplied as 20 mL vials or 50 mL syringes in tamper-evident overwraps. In-use stability for this presentation is assessed under ICH Q1A(R2) with reconstituted time-zero and post-puncture sampling; published data for this specific configuration is limited, so each trial protocol defines the maximum vial dwell time after first broach. No tablet, capsule, or granule presentation is supported for propofol base in this sector because first-pass hepatic extraction prevents a reliable oral solid dose.
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- Propofol Medium and Long Chain Lipid Injectable Emulsion 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.
Propofol Medium and Long Chain Lipid Injectable Emulsion Pharma Grade API is supplied as a sterile oil-in-water dispersed system in which the active substance is dissolved in a mixture of medium-chain triglycerides and long-chain triglycerides, stabilized by purified egg phospholipid, glycerol and sodium oleate. The compendial monograph nomenclature serves as the principal identification rather than a proprietary model number; batch release documentation uses the identifier PLMCT-API-20 for the 20 mg/mL emulsion concentrate and PLMCT-API-10 for the 10 mg/mL presentation. Propofol itself is a hindered phenol with pKa 10.4 and log P approximately 3.8; in the emulsion the active is partitioned between the internal oil phase, the phospholipid interfacial monolayer and the external aqueous phase. The dispersed oil globule carries the active in a thermodynamically metastable state, so globule-size distribution, zeta potential, osmolality, pH, free-propofol aqueous concentration and subvisible particulate burden are controlled as critical quality attributes. The product is intended for use in injectable emulsions and in lipid-based oral solid-dosage intermediates produced by adsorption, spray drying, granulation, or capsule filling.
Release acceptance limits are set around the intact emulsion state as well as chemical purity. The pH is 6.0–8.5, osmolality is 300–330 mOsm/kg, and mean droplet diameter is not more than 220 nm. The large-diameter globule fraction above 5 µm, designated PFAT5, is controlled at ≤0.05% under USP <729> Method II. Propofol content by high-performance liquid chromatography is 98.0–102.0% of label claim. Total related substances are limited to ≤0.5%, and unspecified degradation products are limited to ≤0.10%. The parenteral grade is controlled to <0.6 EU/mg bacterial endotoxin. Residual solvents meet ICH Q3C Option 1 limits, and elemental impurities comply with ICH Q3D parenteral permitted daily exposure limits. The product is terminally sterilized and must meet USP <71> sterility and USP <788> subvisible particulate requirements.
| Parameter | Acceptance limit | Test method |
|---|---|---|
| pH | 6.0–8.5 | Ph Eur 2.2.3 |
| Osmolality | 300–330 mOsm/kg | Ph Eur 2.2.35 |
| Mean droplet diameter | <220 nm | USP <729> Method I, dynamic light scattering |
| Large-diameter globule fraction PFAT5 | ≤0.05% | USP <729> Method II |
| Propofol assay | 98.0–102.0% | HPLC with compendial reference standard |
| Total related substances | ≤0.5% | HPLC area normalisation |
| Unspecified degradation product | ≤0.10% | HPLC |
| Bacterial endotoxin | <0.6 EU/mg | Ph Eur 2.6.14 / USP <85> |
| Sterility | Sterile | Ph Eur 2.6.1 / USP <71> |
| Subvisible particulate matter | Meets USP <788> | Light obscuration particle count |
On production-scale equipment, high-shear mixing must be followed by high-pressure homogenization at 600–900 bar for 3–5 passes. The actual number of passes is not fixed because the target mean diameter and PFAT5 must be confirmed by light-scattering and light-obscuration measurement after each pass. Phospholipid lot-to-lot variation in acid value and peroxide value changes zeta potential and long-term creaming behavior; the stabilizer is pretested before use. The emulsion is blanketed under nitrogen during homogenization and filled under low-oxygen conditions. Terminal moist-heat sterilization can produce slight droplet growth and pH drift; the pre-sterilization pH is therefore set 0.2–0.4 units above the final mid-range so that the sterilized product remains within 6.0–8.5. Inadequate back-pressure during the final homogenization pass produces a bimodal globule-size distribution that may pass the mean droplet diameter test but fail PFAT5; this is a primary batch rejection mode in commercial manufacturing. Temperature excursions above 25°C during fill-finish increase free fatty acid formation and accelerate coalescence. Storage is specified at 2–8°C with no freezing allowed.
Why Are Medium-Chain Triglyceride and Long-Chain Triglyceride Blends Used in Propofol Injectable Emulsions?
The medium-chain triglyceride fraction is composed primarily of caprylic acid and capric acid triglycerides, with chain lengths of C8 and C10. These esters are hydrolyzed more rapidly by lipoprotein lipase than long-chain triglycerides. In the emulsion, the medium-chain fraction lowers oil-phase viscosity and permits more effective shear stress transfer during high-pressure homogenization; the mixed-oil formulation therefore reaches the required mean droplet diameter with fewer passes than a long-chain-oil-only formulation at the same pressure. The long-chain triglyceride fraction provides a larger hydrophobic reservoir for propofol and reduces the aqueous free-propofol fraction compared with a purely medium-chain oil. This balance allows the formulation to combine a smaller and more uniform droplet population with a lower concentration of active in the external aqueous phase.
Published comparisons between medium-chain/long-chain triglycerides and long-chain-only propofol emulsions report a lower incidence of injection-site pain for the mixed-oil formulation, attributed to the reduced aqueous free-propofol concentration. The medium-chain component also enters hepatic oxidation through a carnitine-independent pathway, producing faster plasma triglyceride clearance in parenteral nutrition-related lipid-load models. However, these data are formulation- and study-specific. Bioequivalence and clinical interchangeability must be established independently for each finished product because differences in free propofol concentration, preservative content, and droplet-size distribution can alter pharmacokinetics and local tolerability.
| Property | MCT/LCT mixed-oil grade | LCT-only grade |
|---|---|---|
| Oil-phase composition | Medium-chain triglycerides blended with long-chain triglycerides | Refined soybean or other long-chain triglyceride oil |
| Oil-phase viscosity at 25°C | Lower due to medium-chain fraction | Higher |
| Droplet-size reduction during homogenization | Faster at equivalent pressure | Slower, may require additional passes |
| Aqueous free-propofol fraction | Reduced in mixed-oil dispersion | Higher within the same label concentration |
| Injection-site pain incidence in published studies | Lower observed frequency | Higher observed frequency |
| Triglyceride clearance capacity | Mixed, with medium-chain fraction cleared more rapidly | Long-chain triglyceride clearance only |
Droplet-Diameter Control and the PFAT5 Limit in Terminal Sterilization
The mean droplet diameter is not the sole release criterion. The large-diameter globule fraction above 5 µm is a safety threshold because large globules have reduced capillary passage and are associated with pulmonary fat embolism risk. USP <729> Method I uses dynamic light scattering to characterize the mean and distribution width, while Method II counts the volume-weighted large-diameter globule population. This grade controls PFAT5 to ≤0.05%. Terminal sterilization can increase PFAT5 by 0.01–0.03% depending on autoclave load temperature uniformity; the manufacturing target before sterilization is therefore below 0.04%. The margin accommodates thermal droplet coalescence without exceeding the release limit. During high-pressure homogenization, the final-pass pressure and valve geometry have a stronger effect on PFAT5 than on mean diameter. Batches that meet the 220 nm mean limit but fail PFAT5 typically require a reduction in final-pass back-pressure and an additional recirculation pass at lower temperature.
Zeta potential is controlled as an in-process indicator. In the phospholipid-stabilized emulsion the surface charge is negative at physiological pH because of ionized phosphate groups; values typically fall between -30 mV and -50 mV. If the zeta potential becomes less negative than -20 mV, the formulation is at risk of flocculation. Sodium oleate is included as a co-emulsifier to increase the negative surface charge, but its concentration is controlled because excess co-emulsifier can increase the free aqueous propofol fraction and hemolytic potential. The product is not filtered through a 0.2 µm membrane after terminal sterilization because such filtration can mechanically destabilize the emulsion and alter the label concentration by removing larger lipid globules.
For injectable dilution, 5% glucose injection is the standard admixture diluent. Normal saline and other high-ionic-strength electrolytes compress the electrostatic double layer around the phospholipid-stabilized droplets and can produce creaming or coalescence. The product should not be co-infused with strongly acidic or alkaline drug solutions through the same line without compatibility testing. Freezing is prohibited; storage below 0°C ruptures the oil droplets through ice-crystal penetration, producing irreversible free-oil separation and PFAT5 failure. After first opening, aseptic transfer and use within 24 h are recommended for the parenteral product. Incompatibilities include amine-based additives that raise pH above 8.0, because alkaline conditions accelerate phospholipid hydrolysis and free fatty acid formation. Avoid contact with oxygen and transition-metal ions during processing; oxidation of the unsaturated long-chain triglycerides increases peroxide value and generates rancidity markers that can interact with propofol.
When Tableting, Capsule Filling, or Granulation Is Required for This API
The intact injectable emulsion cannot be directly compressed. For tablet, capsule, or granule use, the liquid lipid load must be converted to a free-flowing powder by adsorption onto porous carriers such as colloidal silicon dioxide, calcium silicate, or dibasic calcium phosphate, or by spray drying with a hydrophilic polymer matrix. If the lipid emulsion fraction exceeds 30% w/w of the dry intermediate, tablet hardness and friability can fall outside pharmacopoeial acceptance limits unless wet granulation or hot-melt granulation is introduced. Capsule filling as a lipid-filled hard capsule or soft gelatin capsule is technically feasible; however, the capsule shell moisture content must be controlled because the emulsion water activity can promote gelatin cross-linking and softening during storage.
Oral administration of propofol is limited by extensive first-pass metabolism, primarily glucuronidation and sulfation in the liver and intestinal mucosa. An oral product based on this API is not a direct bioequivalent substitute for intravenous propofol; it is an investigational delivery system requiring human bioavailability data and controlled-release design to overcome first-pass clearance. Published data for direct compression of intact propofol injectable emulsion into tablets is limited; formulation work is generally confined to spray-dried or adsorbed lipid intermediates. For granules, a low-shear granulation step with a non-aqueous binder is preferred because the emulsion already contains water and additional aqueous binder can exceed the granulation endpoint moisture limit.
Batch release documentation for the oral grade should include water activity, residual moisture, and free propofol aqueous concentration in addition to the compendial release tests. The free-propofol fraction is not a pharmacopoeial monograph parameter but is useful as an in-process control; limits are established during process validation because increases in free active concentration affect both local tolerability and dissolution behavior. The product is not interchangeable with neat propofol API or with a long-chain-triglyceride-only emulsion without formulation and bioequivalence assessment.
