Viloxazine is a centrally acting pharmaceutical active ingredient belonging to the selective norepinephrine reuptake inhibitor (NRI) class. In pharmaceutical products, viloxazine is commonly supplied and formulated as viloxazine hydrochloride, the hydrochloride salt of the active moiety. It is used in the development and manufacture of oral pharmaceutical formulations, particularly extended-release products for the treatment of attention-deficit/hyperactivity disorder (ADHD).
Viloxazine hydrochloride is chemically identified as (RS)-2-[(2-ethoxyphenoxy)methyl]morpholine hydrochloride. It has the molecular formula C13H20ClNO3 and a molecular weight of approximately 273.8 g/mol. The CAS Number of viloxazine hydrochloride is 35604-67-2. FDA records identify the material as a racemic mixture containing one chiral center.
Viloxazine was originally developed as an antidepressant and was used in immediate-release formulations in Europe. Its extended-release formulation was subsequently developed for ADHD. The FDA approved viloxazine extended-release capsules for ADHD, with the active pharmaceutical ingredient present as viloxazine hydrochloride.
Viloxazine Hydrochloride is described as a white to off-white powder. FDA regulatory information reports a melting point of approximately 186.6°C. The substance has one chiral center but is manufactured as a racemic mixture, meaning the pharmaceutical substance contains both enantiomers.
Viloxazine hydrochloride is soluble in water, 0.1 N hydrochloric acid and aqueous solutions with a pH of 9.5 or lower. It is sparingly soluble in methanol, very slightly soluble in acetonitrile, acetic acid and isopropyl alcohol, and practically insoluble in ethyl acetate.
The hydrochloride salt has a pKa of approximately 7.4, which contributes to its aqueous solubility characteristics.
Viloxazine is a selective norepinephrine reuptake inhibitor. It interacts with the norepinephrine transporter (NET), reducing the reuptake of norepinephrine and increasing noradrenergic signaling.
Current FDA information also describes interaction with the 5-HT2C serotonin receptor, where viloxazine exhibits partial agonist activity. The precise mechanism responsible for its therapeutic effects in ADHD has not been completely established.
Viloxazine Hydrochloride is primarily used for pharmaceutical development and manufacturing of oral ADHD medicines.
Major applications include:
FDA-approved extended-release formulations contain viloxazine equivalent to 100 mg, 150 mg and 200 mg of viloxazine free base. These correspond to approximately 115 mg, 173 mg and 231 mg of viloxazine hydrochloride, respectively.
Viloxazine primarily acts by inhibiting the norepinephrine transporter. By reducing norepinephrine reuptake, it increases the availability of norepinephrine within the central nervous system.
FDA pharmacology information reports that viloxazine binds to the norepinephrine transporter and inhibits norepinephrine reuptake. It also has activity at the 5-HT2C receptor.
Viloxazine contains one chiral center. Unlike some pharmaceutical ingredients for which a single enantiomer is selected, viloxazine hydrochloride used in the approved pharmaceutical product is manufactured as a racemic mixture. FDA regulatory documentation explicitly identifies the material as racemic.
This is an important distinction when specifying the API. Viloxazine hydrochloride CAS 35604-67-2 refers to the racemic pharmaceutical substance, while separate CAS numbers exist for the individual R- and S-enantiomers.
Viloxazine Hydrochloride can be characterized using standard pharmaceutical analytical techniques, including:
For commercial pharmaceutical API, identity and purity testing should be performed using validated analytical methods suitable for the applicable regulatory specification.
Viloxazine hydrochloride has significantly different solubility behavior compared with the free-base viloxazine form. The hydrochloride salt is soluble in water and aqueous acidic media.
According to FDA information, it is:
Viloxazine hydrochloride is particularly relevant to extended-release oral dosage forms. The approved extended-release product is designed to provide once-daily administration.
The API is incorporated into a formulation containing excipients that control the release characteristics of the active ingredient. The pharmaceutical development therefore requires appropriate control of API identity, purity, physical properties and consistency.
Viloxazine Hydrochloride intended for pharmaceutical manufacturing should be controlled for:
Because the API is a racemic compound, the stereochemical composition should remain consistent with the approved pharmaceutical material.
Actual commercial acceptance criteria should be based on the manufacturer's validated specification and applicable regulatory filing.
Viloxazine Hydrochloride API is suitable for pharmaceutical companies involved in CNS drug development, ADHD formulations, extended-release oral dosage forms and generic pharmaceutical manufacturing.
The API can support formulation development, analytical research, stability studies and commercial pharmaceutical manufacturing where Viloxazine Hydrochloride is the selected active pharmaceutical ingredient.
Swapnroop Drugs & Pharmaceuticals provides Viloxazine API for pharmaceutical development, formulation and manufacturing requirements, subject to applicable quality and regulatory specifications.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Heavy Metals | NMT 20 ppm |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |
| Melting Point | 185–188°C |