Risdiplam is a synthetic small-molecule survival of motor neuron 2 (SMN2) splicing modifier used in the treatment of spinal muscular atrophy (SMA). It is an orally administered pharmaceutical active ingredient designed to increase production of functional survival motor neuron (SMN) protein by modifying SMN2 pre-mRNA splicing.
Risdiplam has the molecular formula C₂₂H₂₃N₇O and a molecular weight of 401.46 g/mol. The FDA's substance registration system identifies CAS 1825352-65-5 as the primary CAS record for Risdiplam.
Risdiplam is a heterocyclic small molecule chemically identified as 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido-4H-[1,2-a]pyrimidin-4-one.
The API is achiral and has no defined stereocenters. It exhibits pH-dependent aqueous solubility, with substantially greater solubility under acidic conditions. The FDA reports pKa values of 3.78 and 6.62 for Risdiplam.
Risdiplam is used in pharmaceutical products formulated for oral administration, including powder for oral solution and tablets.
| Property | Details |
|---|---|
| API Name | Risdiplam |
| CAS Number | 1825352-65-5 |
| Molecular Formula | C₂₂H₂₃N₇O |
| Molecular Weight | 401.46 g/mol |
| FDA UNII | 76RS4S2ET1 |
| Development Codes | RG-7916, RG7916, RO-7034067 |
| API Type | Synthetic small-molecule API |
| Pharmacological Class | SMN2 splicing modifier |
| Therapeutic Area | Neurology / Genetic Disorders |
| Target | SMN2 pre-mRNA splicing |
| Stereochemistry | Achiral |
| pKa₁ | 3.78 |
| pKa₂ | 6.62 |
FDA substance-registration records confirm the molecular formula, CAS identity and UNII, while the current FDA label confirms the molecular weight and pKa values.
Risdiplam is used for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
SMA is a genetic neuromuscular disorder associated with insufficient production of functional SMN protein. Risdiplam is incorporated into pharmaceutical products intended to increase SMN protein production and thereby address the underlying molecular deficiency associated with 5q SMA. The current U.S. labeling identifies Risdiplam as an SMN2-directed splicing modifier for pediatric and adult patients with SMA.
Risdiplam is available commercially in oral dosage forms, including an oral solution formulation and tablets.
Risdiplam is designed to modify the splicing of SMN2 messenger RNA. In patients with SMA, mutations affecting the SMN1 gene result in insufficient SMN protein. SMN2 can produce some functional full-length SMN protein, but most SMN2 transcripts normally exclude exon 7.
Risdiplam promotes increased inclusion of exon 7 in SMN2 mRNA, resulting in increased production of full-length functional SMN protein. FDA information reports that Risdiplam increases exon 7 inclusion in SMN2 mRNA transcripts and increases full-length SMN protein production in the brain.
Risdiplam API requires comprehensive pharmaceutical quality control covering chemical identity, assay, related substances, residual solvents and physicochemical properties.
Potential analytical controls may include:
FDA CMC documentation for the Risdiplam drug product identifies controls for appearance, assay, related substances, content uniformity and pH, together with microbiological testing for the finished product. These are drug-product controls and should not automatically be represented as universal bulk API specifications.
Because I could not verify a current public USP-NF numerical drug-substance monograph for Risdiplam, unsupported numerical API assay or impurity limits should not be inserted into the CMS specifications.
Risdiplam API manufacturing involves controlled chemical synthesis followed by purification, isolation and drying to obtain pharmaceutical-grade active material.
Manufacturing controls should address starting materials, reaction conditions, process-related impurities, residual solvents, crystallization and final product quality. Because Risdiplam is a relatively complex heterocyclic molecule, appropriate analytical process controls are important for ensuring consistent chemical identity and impurity profiles.
Pharmaceutical manufacturing should be performed under appropriate GMP quality systems with validated analytical methods and documented batch-release procedures.
Risdiplam has a molecular weight of 401.46 g/mol and exhibits pH-dependent aqueous solubility. The FDA states that its greatest solubility occurs at low pH and decreases as pH increases. The reported pKa values are 3.78 and 6.62.
These properties are relevant to formulation development because changes in pH can substantially affect the solubility and dissolution behavior of the API.
The current FDA label describes Risdiplam as the active ingredient in both the oral-solution and tablet presentations of EVRYSDI.
Risdiplam API should be packed in suitable pharmaceutical-grade containers that protect the material from contamination, moisture and inappropriate environmental exposure.
Storage conditions for bulk API should be based on validated stability data and the applicable drug-substance specification. Finished-product storage conditions should not automatically be transferred to bulk API because formulation, packaging and stability characteristics can differ.
Appropriate packaging should preserve API quality throughout transportation and storage while maintaining complete batch traceability.
Pharmaceutical-grade Risdiplam API can be supported with appropriate technical and quality documentation, depending on customer and regulatory requirements:
Risdiplam is a specialized pharmaceutical API requiring controlled chemical synthesis, impurity management and advanced analytical characterization. A reliable Risdiplam API manufacturer in India should maintain robust manufacturing controls, validated analytical methods and appropriate quality systems.
Particular attention should be given to chemical identity, assay, related substances, residual solvents, water content and solid-state characteristics. Consistent manufacturing and comprehensive documentation can support pharmaceutical formulation development and commercial manufacturing of Risdiplam-based products.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |