US Pharm. 2024;49(5):59-60.
Method of Preparation: Calculate the required quantity of each ingredient for the total amount to be prepared. In a mortar, immerse the tablets in a sufficient amount of ORA-Blend for a duration of at least 60 minutes. With the use of a pestle, triturate the tablets into a uniform paste, incrementally integrating the vehicle until a fluid consistency is achieved. Transfer the liquid mixture to a calibrated bottle. Add a small amount of ORA-Blend to the mortar to rinse the mortar of any residue from the drug; then transfer the resulting contents of the mortar to the calibrated bottle. Add additional ORA-Blend to the calibrated bottle to bring the final volume to 200 mL. Shake the mixture well, and then dispense the mixture into an amber bottle.
Use: Clonazepam oral suspension has commonly been used in the treatment of seizures, panic attacks, anxiety disorders, and involuntary muscle spasms.
Packaging: Package mixture in a tight, light-resistant container.
Labeling: Keep out of reach of children. Shake well. Discard after ____ [time period].
Stability: The USP default beyond-use date for nonpreserved aqueous oral liquids is 14 days when stored at controlled room temperature.1 However, according to additional stability studies, this extemporaneous oral suspension is stable for up to 60 days when stored at 5°C to 25°C.2
Quality Control: Weight/volume, pH, specific gravity, active drug assay, color, rheologic properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, and mold growth) are all considered examples of quality-control assessments.3
Discussion: Clonazepam, which is a benzodiazepine, is prescribed for a variety of conditions, including anxiety, panic disorder, seizures, and insomnia. Clonazepam works by amplifying the activity of gamma-aminobutyric acid (GABA), which, as the most important inhibitory neurotransmitter in the central nervous system, suppresses or regulates many neurotransmissions and neurons. GABA is synthesized by the interaction of the amino acid glutamate with the enzyme glutamic acid decarboxylase. GABA plays a critical role in the pathophysiology of anxiety spectrum disorders. By enhancing GABA activity, clonazepam reduces anxiety and promotes relaxation while also potentially improving sleep quality and decreasing the frequency and intensity of seizures. In general, benzodiazepines act by augmenting GABA activity at the GABAA receptor, leading to sedative, hypnotic, anxiolytic, anticonvulsant, and muscle-relaxant effects. Serious adverse effects of clonazepam use include confusion, hallucinations, suicidal ideation, respiratory depression, and exacerbation of seizures.
Commercially available as tablets in strengths of 0.25 mg, 0.5 mg, 1 mg, and 2 mg, clonazepam (Klonopin, C15H10ClN3O3, MW 315.7) is available as a light yellow, crystalline powder. Clonazepam demonstrates rapid and near-complete absorption upon oral administration, with peak plasma concentrations reached within 1 to 4 hours and an absorption half-life of approximately 25 minutes. Clonazepam exhibits limited solubility in water (<100 mg/L at 25°C), and it is insoluble in benzene; additionally, it demonstrates slight solubility in acetone, methanol, and chloroform.4,5
ORA-Blend is a sweetened vehicle that is commonly utilized in the compounding of oral preparations. This vehicle is specifically designed to improve the taste and stability of oral suspensions. ORA-Blend consists of a synergistic blend of suspending agents with high colloidal activity that form a gel-like matrix that effectively suspends particles while minimizing settling. The formulation is buffered to a slightly acidic pH, which helps reduce the oxidative degradation of medicinal agents. ORA-Blend also contains antifoaming agents, thereby permitting vigorous shaking with minimal foam formation, which ensures proper medication dispersion within the suspension.6
REFERENCES
1. U.S. Pharmacopeia/National Formulary [current revision]. Rockville, MD: U.S. Pharmacopeial Convention, Inc; September 2022.
2. Allen LV Jr, Erickson MA III. Stability of acetazolamide, allopurinol, azathioprine, clonazepam, and flucytosine in extemporaneously compounded oral liquids. Am J Health Syst Pharm. 1996;53:1944-1949.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
4. Klonopin (clonazepam) product information. South San Francisco, CA: Genentech USA, Inc; October 2013.
5. PubChem. Compound summary: clonazepam. https://pubchem.ncbi.nlm.nih.gov/compound/Clonazepam. Accessed April 9, 2024.
6. ORA-Blend product information. Minneapolis, MN: Padagis LLC; 2022.
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