Albendazole (54965-21-8) Physical and Chemical Properties
Albendazole
Broad‑spectrum benzimidazole anthelmintic API commonly handled in pharmaceutical development, formulation and QC for antiparasitic products.
| CAS Number | 54965-21-8 |
| Family | Benzimidazoles |
| Typical Form | Powder / crystalline solid |
| Common Grades | BP, EP, FCC, USP |
Albendazole is a synthetic benzimidazole‑carbamate anthelmintic. Chemically it is a methyl carbamate ester of a 2‑benzimidazolyl scaffold substituted at the 5‑position with a propylsulfanyl (propylthio) group; the structure combines an aromatic bicyclic heterocycle (benzimidazole) with a polar carbamate ester and a lipophilic thioalkyl substituent. The benzimidazole core provides the canonical tubulin‑binding pharmacophore found across benzimidazole anthelmintics, while the carbamate functionality and S‑alkyl substituent modulate solubility, metabolic S‑oxidation and tissue distribution.
Electronically the molecule is overall neutral (formal charge 0) and contains heteroatoms that create mixed polarity: hydrogen‑bonding donors (two NH environments available for intermolecular hydrogen bonding in the benzimidazole/carbamate region) and multiple acceptor sites (carbonyl and heterocyclic nitrogen atoms). Topological polar surface area and hydrogen‑bonding counts indicate moderate polarity that, combined with a modest octanol–water partition coefficient, gives low aqueous solubility with appreciable tissue partitioning and oral absorption variability.
Pharmacokinetic and chemical behaviour is dominated by rapid hepatic S‑oxygenation and oxidative metabolism at the sulfide side chain to the active sulfoxide and subsequently to sulfone metabolites; the sulfoxide is the principal systemic anthelmintic species. The parent carbamate is poorly water soluble and shows limited direct plasma exposure after oral dosing unless coadministration with food (especially fatty meals) enhances bioavailability. Clinically and industrially, albendazole is an established broad‑spectrum anthelmintic used in human and veterinary medicine against nematodes and cestodes and appears in solid oral formulations (tablets) at defined dose strengths for systemic and intestinal indications.
Common commercial grades reported for this substance include: BP, EP, FCC, USP.
Basic Physicochemical Properties
Density and Solid-State Form
Physical description: Solid; reported as colorless crystals. The substance is provided and handled as a crystalline solid in standard pharmaceutical and analytical contexts; particle morphology and polymorphism can influence dissolution rate and formulation performance.
Melting Point
Experimental melting point values reported in supplied characterizations include: 208-210, 208-210 °C, 209 °C (multiple determinations). A related oxidative metabolite (albendazole sulfoxide) has reported melting behaviour described as "MP: 226-228 °C (decomposes) /Sulfoxide/". These values reflect the high melting, crystalline nature of the parent carbamate and the different thermal stability of S‑oxidized derivatives.
Solubility and Dissolution Behavior
Measured aqueous solubility is extremely low; reported values include "1.4 [ug/mL] (The mean of the results at pH 7.4)", an additional listing as "Practically insoluble", and "2.28e-02 g/L". Low aqueous solubility is consistent with the combination of an aromatic heterocycle and a lipophilic propylthio substituent and explains variable and often poor oral absorption unless dosing is accompanied by a fatty meal to enhance dissolution and biliary solubilization. In formulation development, strategies to improve systemic exposure commonly target solubilization (lipid co‑administration, micronization, solid dispersions) or conversion to more soluble salts/prodrugs where applicable.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
No experimentally established value for this property is available in the current data context. Qualitatively, the molecule contains a benzimidazole heterocycle (heterocyclic N–H/basic site) and a neutral carbamate ester; the overall compound is described as neutral under typical conditions. The benzimidazole moiety is the primary site that can accept a proton (conjugate acid formation) in strongly acidic media, while the carbamate ester remains essentially non‑ionized across physiological pH. Practically, albendazole exists predominantly as a neutral species at physiological pH, contributing to its low aqueous solubility and reliance on formulation or food effects to improve absorption.
Reactivity and Stability
Albendazole is chemically stable as a crystalline solid under ambient conditions but is susceptible to oxidative S‑oxygenation and photolysis. Biotransformation proceeds rapidly in hepatic systems to albendazole sulfoxide (the principal active metabolite) and further to albendazole sulfone; these S‑oxygenation steps are catalysed by flavin monooxygenases and cytochrome P450 enzymes. Environmentally and in photochemical experiments, direct photolysis in sunlit water is rapid: measured half‑lives for direct photolysis in sunlit water are reported as 10, 16 and 6 minutes at pH 5, 7 and 9 respectively under summer conditions (and 50, 80 and 20 minutes under winter conditions). Hydrolytic degradation of the neutral parent is slow under neutral to basic conditions in abiotic systems: estimated base‑catalysed hydrolysis corresponds to half‑lives on the order of decades to centuries (examples reported include estimated half‑lives of 840 and 84 years at pH 7 and pH 8, respectively, from structural estimation methods), indicating the carbamate function is relatively resistant to nonenzymatic hydrolysis. In practical use, oxidative metabolism and enzymatic S‑oxidation dominate transformation; formulation and storage should minimize exposure to strong oxidants and prolonged light to reduce product degradation.
Molecular Parameters
Molecular Weight and Formula
Molecular formula: C12H15N3O2S
Molecular weight: 265.33 (as reported).
Exact/monoisotopic masses reported: 265.08849790 (ExactMass / MonoisotopicMass).
LogP and Structural Features
Computed XLogP3: 2.9 (computed descriptor). Experimental logP/log Kow data reported include values of 2.7 and a log Kow = 1.27 (both experimental determinations are reported in different contexts). The molecular profile — an aromatic benzimidazole ring, a methyl carbamate and a propylthio substituent — yields moderate lipophilicity balanced by polar heteroatoms; this combination produces modest membrane permeability but low aqueous solubility. Key computed descriptors: Topological Polar Surface Area (TPSA) = 92.3; Hydrogen bond donor count = 2; Hydrogen bond acceptor count = 4; Rotatable bond count = 5; Formal charge = 0; Complexity = 290. These metrics align with a small‑molecule drug that is neutral, moderately polar at the molecular surface, and amenable to formulation strategies to enhance bioavailability.
Structural Identifiers (SMILES, InChI)
SMILES: CCCSC1=CC2=C(C=C1)N=C(N2)NC(=O)OC
InChI: InChI=1S/C12H15N3O2S/c1-3-6-18-8-4-5-9-10(7-8)14-11(13-9)15-12(16)17-2/h4-5,7H,3,6H2,1-2H3,(H2,13,14,15,16)
InChIKey: HXHWSAZORRCQMX-UHFFFAOYSA-N
(Identifiers are provided in plain text as structural descriptors for informatics and analytical matching.)
Identifiers and Synonyms
Registry Numbers and Codes
CAS: 54965-21-8
European Community (EC) Number: 259-414-7
UNII: F4216019LN
ChEBI: CHEBI:16664
ChEMBL: CHEMBL1483
DrugBank: DB00518
NSC Number: 758644 (also listed as NSC-220008 / NSC758644 in some contexts)
KEGG: C01779 (drug), D00134 (compound)
InChIKey: HXHWSAZORRCQMX-UHFFFAOYSA-N
Synonyms and Brand-Independent Names
Reported nonproprietary and commonly used synonyms include: albendazole; Albenza; Zentel; Valbazen; Eskazole; Andazol; Bilutac; SKF‑62979 / SK&F‑62979; methyl 5-(propylthio)-2-benzimidazolecarbamate; methyl N-(5‑propylsulfanyl-1H-benzimidazol-2-yl)carbamate. Multiple additional supplier and registry synonyms exist for analytical standards and formulations; the list above includes the principal generic and pharmaceutical identifiers encountered in manufacturing and regulatory contexts.
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Albendazole is used as the active pharmaceutical ingredient (API) in human and veterinary anthelmintic products. It functions principally as a tubulin‑binding microtubule inhibitor in susceptible helminths and is administered orally for systemic and intestinal parasitic infections. The compound is included in essential medicines lists for treatment of several parasitic diseases and is formulated into solid oral dosage forms (tablets) for clinical use. It is not typically used as a synthetic intermediate in broader synthetic chemistry beyond analog development for anthelmintic research.
Formulation and Development Contexts
Commercial solid oral formulations are specified in standard dosage strengths: examples cited include chewable tablets at 400 mg (scored) and 200 mg (chewable). Oral bioavailability is low owing to limited aqueous solubility of the parent; this property is routinely addressed in clinical dosing guidance by recommending administration with a fatty meal to increase exposure to the active sulfoxide metabolite. Formulation strategies in development or quality control focus on particle size reduction, optimized excipient selection, and stability under light/oxidative stress to control degradation to sulfoxide/sulfone and to achieve consistent dissolution and systemic exposure.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Typical grade concepts applicable to albendazole include: pharmaceutical (API) grades intended for use in drug product manufacture, analytical reference standards for assay and identity testing, and technical grades for veterinary or research use. Selection of a specific grade depends on regulatory and compendial requirements for the intended application.
Under detected commercial grades, the substance is reported with the following grade labels: BP, EP, FCC, USP.
General Quality Attributes (Qualitative Description)
Quality attributes for albendazole relevant to procurement and QC include identity (SMILES / InChI / InChIKey), assay content (typically defined by the pharmacopeial monograph for the selected grade), polymorphic/crystalline form (which affects melting point and dissolution), residual solvents and heavy metals limits, and specified limits for related substances (including S‑oxidation products such as the sulfoxide and sulfone). For pharmaceutical API grading, typical controls cover water content, particle size distribution, assay by HPLC, and tests for impurities and residual catalysts when applicable. Analytical standards and reference materials are supplied with certificates of analysis documenting these attributes.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
Albendazole has a pharmacology‑linked toxicology profile: it is an anthelmintic that can produce reversible elevations of hepatic enzymes in a significant fraction of treated patients and has been associated, rarely, with clinically apparent hepatotoxicity including severe outcomes. Reported serious toxicities include hepatotoxicity and bone‑marrow suppression (leukopenia, agranulocytosis, pancytopenia) in rare cases; blood counts and liver function monitoring are recommended for prolonged or repeated courses. It is also associated with reproductive toxicity in animal studies and is contraindicated in pregnancy unless benefit justifies risk; therefore pregnancy testing and contraception guidance are typical risk‑mitigation measures in clinical use.
Acute toxicity data include an LD50 reported as \(1500\,\mathrm{mg}\,\mathrm{kg}^{-1}\) (oral, mouse) (MSDS‑style reporting). Common adverse effects include headache and transient increases in serum aminotransferases; other effects observed include gastrointestinal upset, hypersensitivity reactions, and rare reversible alopecia. Protein binding of the active metabolite (albendazole sulfoxide) is reported at approximately 70% which contributes to its distribution profile and drug‑drug interaction potential. Enzyme induction potential (cytochrome P450 induction) and interactions that alter sulfoxide exposure (e.g., corticosteroids, praziquantel) should be considered when co‑administering.
For hazard communication, reported classifications across notification summaries include skin and eye irritation, respiratory irritation potential, and reproductive toxicity hazard statements in some submissions; workplace handling should assume potential for dermal and respiratory exposure and reproductive hazard until proper risk assessment of the supplied material is performed.
Storage and Handling Guidelines
Handle albendazole as a pharmaceutical active substance with appropriate industrial hygiene controls: use local exhaust ventilation or containment to limit dust generation; wear suitable personal protective equipment (gloves, eye protection and respiratory protection where airborne dust may be generated); avoid ingestion, inhalation and dermal contact. Store in a cool, well‑ventilated, dry area protected from light and oxidants; container closure should be secure to prevent moisture uptake and minimize oxidative exposure that may promote S‑oxidation or other degradative pathways. For transport, disposal and regulatory compliance, consult the product‑specific Safety Data Sheet (SDS) and applicable local legislation. In clinical settings, monitor liver function tests and blood counts as clinically indicated and observe pregnancy‑related contraindications.
For detailed hazard, transport and regulatory information, users should refer to the product-specific Safety Data Sheet (SDS) and local legislation.
