| HS Code | 582564 |
| Product Name | Pimavanserin Tartrate Pharma Grade API |
| Chemical Name | 1-(4-Fluorophenyl)-1-[(1-methylpiperidin-4-yl)methyl]-3-[4-(2-methylpropoxy)benzyl]urea L-tartrate |
| Cas Number | 706782-28-7 |
| Molecular Formula | C29H40FN3O8 |
| Molecular Weight | 577.64 g/mol |
| Grade | Pharma Grade |
| Appearance | White to off-white crystalline powder |
| Solubility | Soluble in water and methanol; sparingly soluble in ethanol; practically insoluble in non-polar organic solvents |
| Assay | 98.0% to 102.0% on dried basis |
| Residual Solvents | Complies with ICH limits |
| Storage Conditions | Store in tightly closed container below 25°C, protected from light and moisture |
As an accredited Pimavanserin Tartrate 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 | Pimavanserin Tartrate Pharma Grade API is packed in 25 kg drums with double polyethylene liners, ensuring stability for oral and injectable formulations. |
| Container Loading (20′ FCL) | 20' FCL container loading of Pimavanserin Tartrate Pharma Grade API, suitable for tablet, capsule, granule, oral, and injectable formulations. |
| Shipping | Pimavanserin Tartrate Pharma Grade API is shipped in sealed, double-lined containers with desiccants to prevent moisture and contamination. Cold-chain or temperature-controlled transport is available for stability. Shipments include complete documentation, traceability, and compliance with IATA/IMDG regulations for safe, secure global delivery. |
| Storage | Store Pimavanserin Tartrate Pharma Grade API in a tightly sealed, original container protected from light, moisture, and heat. Keep in a cool, dry, well-ventilated area at controlled room temperature, 15–30°C (59–86°F). Avoid exposure to incompatible substances. Ensure container remains closed when not in use and use within expiry after opening. |
| Shelf Life | Shelf Life: 24 months from manufacturing date when stored in tightly closed containers, protected from light, moisture, and heat. |
In low-dose immediate-release tablet development for pimavanserin tartrate, the selection of direct compression, wet granulation, or roll compaction is governed by the API particle size distribution and the segregation tendency of a 34 mg base-equivalent dose after geometric preblending. Pimavanserin tartrate is described in reference labelling as slightly soluble in water, which imposes a dissolution-limited absorption boundary in immediate-release solid oral dosage forms and makes particle size control more influential than bulk drug assay alone. Direct compression feasibility typically begins with a 1:10 API-diluent preblend passed through a 425 µm screen, followed by blending in a bin blender at 10–15 rpm for 15–20 min; blend uniformity is confirmed against USP <905> with acceptance value ≤ 15.0. Compression on a rotary tablet press with main compression force between 8 kN and 12 kN has been evaluated to achieve tablet hardness of 60 N to 90 N and disintegration below 5 min per USP <701>. The principal process conflict in direct compression is segregation of the active from lactose monohydrate or mannitol during hopper discharge, particularly when the API fraction is below 10% w/w. Wet granulation reduces segregation but introduces a moisture-exposed processing window; for a high-shear granulator with an impeller tip speed of 4–6 m/s and water addition of 20–25% w/w, endpoint torque must be monitored because overgranulation can shift the granulate size distribution above 850 µm and retard dissolution. Loss on drying is controlled at 1.5–2.5% w/w before milling through a 0.8 mm screen. Roll compaction, when used as a dry granulation alternative, should be controlled by ribbon density measurements; a target ribbon density range of 1.15–1.25 g/cm³ and milled granulate fraction between 180 µm and 850 µm are typical feasibility starting points for low-dose tartrate salt formulations, though published data for this specific configuration is limited.
| Process route | Representative equipment type | Control parameter | Observed failure mode at limit boundary |
|---|---|---|---|
| Direct compression | Rotary tablet press, gravity-induced hopper feed | Main compression force 8–12 kN | Blend segregation, content uniformity AV > 15.0 |
| High-shear wet granulation | Top-driven high-shear granulator | Water addition 20–25% w/w, LOD 1.5–2.5% w/w | Over-granulation, dissolution deceleration at pH 6.8 |
| Fluid-bed granulation | Glatt GPCG class unit, top-spray nozzle | Inlet air temperature 55–65 °C, product temperature 30–38 °C, spray rate 8–12 g/min | Spray drying of binder rather than agglomeration, low granulate yield |
| Roll compaction | Gerteis or Alexanderwerk roller compactor | Ribbon density 1.15–1.25 g/cm³ | Ribbon brittleness, excessive fines < 180 µm, poor tablet hardness |
The tartrate moiety in pimavanserin tartrate is less hygroscopic than hydrochloride counterparts, but hard gelatin capsule shells still present a measurable crosslinking risk when low-moisture granulate is filled under dry finishing conditions. In a 34 mg base-equivalent capsule filled to a formulation-specific total mass, powder blend bulk density should remain between 0.45 g/cm³ and 0.65 g/cm³ with a Carr index between 15% and 25% to maintain dosator or tamping-pin filling consistency. Content uniformity is assessed by USP <905>; weight variation acceptance is typically not more than 10% RSD for low-dose capsules. The more serious stability boundary is aldehyde-mediated gelatin crosslinking, which can produce a pellicle during dissolution testing at pH 6.8 because the capsule shell fails to rupture uniformly. The operational boundary is moisture: hard gelatin shells embrittle when stored below 40% relative humidity, yet residual moisture in granulate above 2.0% w/w can hydrolyze tartrate salt and increase free acid microenvironment pH. Desiccant loading should therefore be calculated from the sorption isotherm of the filled capsule, not from fixed unit count. If crosslinking is observed as a two-stage dissolution plateau in USP <711> apparatus 2 at 50 rpm, replacement of gelatin with HPMC capsules or reformulation with non-reducing diluents such as mannitol is the established correction; published data for pimavanserin tartrate in gelatin capsules is limited to the reference product and does not define a generic desiccant limit.
For granules intended for reconstitution in oral suspension or for sprinkle administration to patients with Parkinson’s-related dysphagia, the controlling physical attribute is mouthfeel-defined particle size rather than compressibility. A D90 ceiling of 500 µm prevents gritty residue after swallowing, while a D10 floor near 40 µm limits dust formation and dose loss during sachet filling. Fluid-bed top-spray granulation with a hypromellose E5 binder at 3–5% w/w, atomization air pressure of 1.5–2.0 bar, inlet air temperature of 55–65 °C, and product temperature of 30–38 °C is the conventional route to agglomerate the API with mannitol or isomalt. Suspension rheology is adjusted with xanthan gum at 0.3–0.8% w/v to produce apparent viscosity between 50 mPa·s and 150 mPa·s at 25 °C and a shear rate of 10 s⁻¹. Sedimentation volume after 24 h should exceed 0.9; otherwise resuspendability fails and dose accuracy from a bottle adapter becomes unacceptable. Preservative selection in aqueous suspensions must account for tartrate salt partitioning: methylparaben and propylparaben are typical, but assay recovery above 98% after 7 days at 25 °C and 60% relative humidity must be demonstrated before locking the formula. The tartrate salt can also depress the pH of reconstituted suspension into the range where taste masking with citric acid buffer at pH 4.0–5.0 is required, but excessive buffer strength increases ionic strength and accelerates sedimentation; this trade-off is the primary formulation conflict for granule suspensions.
A candidate sterile injectable solution containing pimavanserin tartrate must be evaluated against the solubility-limited boundaries of the tartrate salt at pH values compatible with parenteral administration. The reference product is not labelled as an injectable, so an injectable development path relies on API solubility at low pH and forced degradation data under ICH Q1B. Aqueous solubility of pimavanserin tartrate is improved below pH 3.0, but pH values below 4.0 can cause local injection-site tolerability limits and require acetate or citrate buffering. Aseptic filtration through a 0.22 µm PVDF membrane is the standard sterilizing-grade operation; adsorptive loss must be measured because low-dose pimavanserin tartrate can bind to membrane surfaces, with recovery below 90% triggering filter compatibility review under FDA 21 CFR 211.84. If terminal moist heat sterilization is considered, a minimum F₀ of 8 min at 121 °C must be justified by assay recovery and impurity profiling; forced degradation studies may reveal an assay loss boundary that makes aseptic processing the only acceptable route. Injectable control tests include subvisible particulate matter by USP <788> with light obscuration limits of not more than 6000 particles per container at ≥10 µm and not more than 600 particles per container at ≥25 µm, osmolality by USP <785>, and bacterial endotoxin by USP <85>. The endotoxin limit is dose-calculated from patient exposure; no public monograph fixes a product-specific value for pimavanserin tartrate injection. Container closure compatibility with USP <381> elastomeric closures must be confirmed because tartrate salt formulations can extract zinc and sulfur-containing accelerators from rubber stoppers when stored at 40 °C for 4 weeks.
| Test attribute | Applicable standard | Typical action limit |
|---|---|---|
| Filter integrity pre- and post-filtration | Manufacturer bubble point specification | Failure of bubble point test rejects batch |
| Subvisible particulate matter | USP <788> | Not more than 6000 particles ≥ 10 µm, 600 particles ≥ 25 µm per container |
| Osmolality | USP <785> | Formulation-specific, typically 270–330 mOsm/kg for isotonicity |
| Bacterial endotoxin | USP <85> | Calculated from maximum patient dose; no public monograph value |
| Sterility | USP <71> | No growth in 14 days |
A fixed-dose combination of pimavanserin tartrate with levodopa is not a registered monograph, but process feasibility screening requires stability-driven excipient selection because levodopa contains a primary amine and can undergo Maillard-mediated discoloration with reducing sugars. Lactose monohydrate is therefore replaced by mannitol or isomalt in binary mixture studies. Forced degradation screening of a binary mixture at 40 °C and 75% relative humidity for 4 weeks under ICH Q1B conditions is the minimum data set before formula locking. If tartrate salt lowers the microenvironmental pH below 5.0, browning may be accelerated, while pH above 6.0 accelerates levodopa oxidation; this narrow pH window is the critical process boundary. Dry granulation by roll compaction is preferred over aqueous wet granulation because the latter can generate a reactive amorphous levodopa surface and increase impurity formation. The operational boundary for the granulate is a moisture content below 2.0% w/w and storage with desiccant to maintain headspace relative humidity below 30%. Published data for this specific fixed-dose configuration is limited; therefore the formulation must be developed against measured impurity indices rather than assumed compatibility.
Competitive Pimavanserin Tartrate 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!
Article PIM-T-API-01 is a pharma-grade pimavanserin tartrate active pharmaceutical ingredient supplied as a white to off-white powder for formulation into tablets, capsules, granules, and injectable dosage forms. The substance is chemically described as N-[(4-fluorophenyl)methyl]-N-(1-methylpiperidin-4-yl)-N′-[4-(2-methylpropoxy)phenyl]methylurea hemi-tartrate. It carries CAS 706782-28-7 and corresponds to the molecular formula C25H34FN3O2·0.5C4H6O6, commonly calculated as C27H37FN3O5 with a relative molecular mass of 502.61 g/mol. The free base, CAS 706779-91-1, has a relative molecular mass of 427.55 g/mol. Each 40 mg of the hemi-tartrate supplies approximately 34 mg of pimavanserin free base, which is the basis of the labelled content in the reference oral capsule formulation. The salt factor is therefore 1.176, and all assay calculations must be corrected to the anhydrous, solvent-free hemi-tartrate entity rather than the free base. The API is not a sterile product as supplied; injectable applications require downstream sterile filtration, aseptic fill, or terminal sterilization that must be validated according to the finished-product regulatory file.
Release testing is controlled under a pharmacopoeial monograph where available and reinforced with ICH-defined impurity thresholds. The representative specification for Article PIM-T-API-01 is summarized for the micronized oral grade; injectable-evaluation material may carry lower bioburden and endotoxin requirements and is qualified by the finished-product manufacturer against the parenteral dosage-form criteria.
| Parameter | Acceptance criterion | Reference method |
|---|---|---|
| Appearance | White to off-white powder | Visual examination |
| Identification A | IR spectrum conforms to reference standard | USP <197> |
| Identification B | HPLC retention time conforms to reference standard | USP <621> |
| Assay | 98.0%–102.0% of C27H37FN3O5 on anhydrous and solvent-free basis | HPLC, USP <621> |
| Related substances | Any unspecified impurity ≤0.10%; total impurities ≤1.0% | HPLC area normalization, ICH Q3A |
| Water content | ≤1.0% | Karl Fischer, USP <921> |
| Residue on ignition | ≤0.1% | USP <281> |
| Elemental impurities | Class 1, 2A, 2B, and 3 limits according to ICH Q3D | USP <232>/<233> |
| Residual solvents | Process-specific limits according to ICH Q3C | Headspace GC, USP <467> |
| Particle size, micronized grade | D90 ≤20 μm; D50 3–8 μm | Laser diffraction, ISO 13320 |
| Crystalline form | Conforms to reference diffractogram; no extraneous crystalline form | XRPD |
| Microbial limits, non-sterile oral grade | Total aerobic microbial count ≤1000 CFU/g; combined yeast and mould ≤100 CFU/g; Escherichia coli absent | USP <61>/<62> |
| Bacterial endotoxins, injectable evaluation grade | Must meet finished-product parenteral limit; typical endotoxin testing is performed during injectable qualification | USP <85> |
The HPLC related-substances method is validated according to ICH Q2(R1), with peak purity assessed by photodiode array or mass spectrometry for stressed samples. Method sensitivity must allow reliable integration at the reporting threshold of 0.05%, and the impurity profile is compared against forced-degradation studies using heat, acid, base, oxidation, and light. Forced-degradation conditions used to support the related-substances method include 0.1 N hydrochloric acid, 0.1 N sodium hydroxide, 3% hydrogen peroxide, dry heat at 105 °C, and photolysis according to ICH Q1B. Residual solvent control is process-specific; if the final crystallization uses ethanol or isopropyl acetate, the corresponding limits are taken from ICH Q3C. Elemental impurity data are provided in the technical pack, with particular attention to palladium or other transition-metal catalysts that may be used in synthetic steps; control is by ICP-MS.
Control of particle size is the principal variable for solid oral processing. Micronized material with D90 ≤20 μm is preferred when the developer requires direct compression or dry granulation, because the hemi-tartrate salt is usually formulated at low drug load. Milling is performed on an air-jet mill equipped with inert-gas cooling to limit amorphous surface generation. X-ray powder diffraction is used before and after milling to confirm that the crystalline polymorph has not converted; the acceptance criterion is conformity of the diffractogram to the approved reference pattern. Differential scanning calorimetry is used as a supporting identity and solvate screen, with the thermogram recorded from 25 °C to 250 °C at 10 °C/min under nitrogen purge.
For tablet and capsule development, the API is typically pre-blended with a portion of filler in a bin blender before direct compression or granulation. Blend uniformity is assessed by stratified sampling; finished dosage units are tested according to USP <905> and dissolution according to USP <711>. If a wet granulation route is selected, the binder solution is added at a controlled spray rate, and the granulate is dried to a target moisture content determined by Karl Fischer. Drying endpoint is confirmed by loss on drying and by XRPD to ensure that no hydrate or amorphous form develops. On production-scale lines, direct compression may show segregation when API particle size is not matched to excipient particle size; this failure mode is generally detected by high relative standard deviation in blend samples and by content uniformity results that approach the USP <905> acceptance value limit.
For capsule filling, the material is dry-mixed with a flow aid and a lubricant. Automatic dosator or tamping-pin capsule machines require consistent powder bed height and low electrostatic charge. Granulation is used when the powder compressibility index exceeds 25% or the Hausner ratio exceeds 1.34, which indicates poor flow. Roller compaction is an alternative when the API is moisture-sensitive; ribbon density and mill screen size must be controlled to avoid fines generation. Granule presentations intended for sachet or reconstitution require the same particle-size discipline, together with a dissolution method that can detect agglomerated or poorly wetting granules. Wet granulation with a high-shear granulator is generally run to a target torque or power-consumption endpoint rather than a fixed time, because granule growth varies with batch-to-batch differences in particle size and moisture.
Pimavanserin tartrate is differentiated from conventional antipsychotic APIs by its primary receptor pharmacology. It acts as a selective serotonin 5-HT2A inverse agonist and does not depend on dopamine D2 receptor occupancy for the treatment of Parkinson's disease psychosis; the reference listed oral product is approved in the United States for hallucinations and delusions associated with Parkinson's disease psychosis at 34 mg pimavanserin once daily. This contrasts with quetiapine fumarate, risperidone, olanzapine, and haloperidol, which exert dopamine D2 antagonism and may worsen motor function in the Parkinson's disease population.
The salt form also differs from other antipsychotic APIs. Pimavanserin tartrate is supplied as a hemi-tartrate with a salt factor of 1.176, whereas quetiapine is supplied as a fumarate salt and haloperidol as the base or decanoate ester. This affects conversion calculations for label-claim content, salt correction in assay, and dissolution media selection. For compendial methods, the assay must be calculated against C27H37FN3O5, not against the free base, otherwise the result will be systematically shifted by approximately 15%. Pharmacokinetically, pimavanserin is metabolized primarily by CYP3A4 and CYP3A5. Finished-product labeling therefore restricts coadministration with strong CYP3A4 inhibitors and inducers; this is not an API physicochemical specification but a formulation-development constraint.
Injectable-grade evaluation begins with bacterial endotoxin control, because the tartrate material supplied for oral use is not routinely released against parenteral bioburden limits. The dissolved API solution must comply with USP <71> sterility, USP <85> bacterial endotoxins, and USP <788> particulate matter after aseptic filtration through a 0.22 μm filter. Formulation pH and buffer species should be selected to maintain chemical stability; published data for specific parenteral formulations of pimavanserin tartrate is limited. The free-base lipophilicity can require solubility-enhancing excipients in injectable vehicles, but the tartrate salt has a higher aqueous dissolution rate than the free base under comparable pH conditions. Terminal sterilization is preferred when product stability supports it; otherwise aseptic processing with filter integrity testing according to the finished-product batch record is required. Silicone tubing, glass delamination, and stopper fragmentation are the principal particulate sources that must be excluded by compatibility and stability studies.
The API should be stored in tightly closed, light-resistant containers at 20–25 °C, with excursions permitted to 15–30 °C. High-humidity open handling is not recommended because moisture can alter powder flow and may promote surface amorphous content; where open exposure exceeds 60% relative humidity, pre-drying under vacuum at 40 °C should be validated by X-ray powder diffraction before and after drying. The substance is incompatible with strong oxidizing agents and should not be exposed to strong acids or bases that may hydrolyze the urea linkage. Changeover validation on shared lines should include cleaning verification with an analytical method capable of quantifying residues below 10 ppm or 1/1000 of the therapeutic dose, whichever is lower, consistent with risk-based cleaning validation. Dedicated or segregated scoops, sieves, and compression tooling should be used where practical to reduce cross-contamination risk during oral-dosage development.
