สารบัญ

Thai name  ยาน้ำมันกัญชาหยอดใต้ลิ้น (YA NAM MAN KANCHA YOT TAI LIN)

Category  Anti-emetic; anti-epileptic; analgesic.

Cannabis Sublingual Drops are the Cannabis Extract in a suitable vegetable oil such as sesame oil, olive oil or coconut oil. They contain not less than 90.0 per cent and not more than 110.0 per cent of the labelled amounts of tetrahydrocannabinol (C₂₁H₃₀O₂) or cannabidiol (C₂₁H₃₀O₂) or a mixture thereof.

Description  Pale yellow to brownish yellow oily liquid; odour, characteristic.

Strengths available  Cannabidiol 100 mg per mL; tetrahydrocannabinol 10 and 17 mg per mL; 27 mg of tetrahydrocannabinol and 25 mg of cannabidiol per mL.

Dose  Instill under the tongue, as directed by a physician.

Other relevant information
1. Cannabis sublingual drops must be used under strict supervision of a physician as they are still considered narcotics under Category 5 of the Narcotics Act B.E. 2522 (1979).
2. It is contra-indicated in patients with a known history of hypersensitivity to cannabis extract or any ingredients in the formulation, as well as those with unstable cardio-pulmonary diseases or having risks for cardiovascular diseases.
3. Risk-benefit should be considered if it is to be used in pregnant or nursing women, adolescents and patients with a known history of mental illnesses or compromised cardiovascular and/or respiratory symptoms.
4. It may cause dizziness, vomiting, urinary tract infections, relapsing multiple sclerosis, bradycardia, and/or abnormal blood pressure. Therefore, dose reduction may be required.
5. Drowsiness or light-headedness may occur which may impair the ability to drive or perform other tasks requiring alertness.
6. Cannabis therapy should be promptly discontinued if disorientation, agitation, anxiety, hallucination, and/or psychosis occur.

Packaging and storage Cannabis Sublingual Drops shall be kept in tightly closed containers, preferably in amber glass containers, protected from light, and stored at a temperature not exceeding 25º.

Labelling The label on the container states the amounts of tetrahydrocannabinol and/or cannabidiol.

Identification
     A. To 500 mg of the sample in a screw-capped, amber test-tube, add 10 mL of a mixture of 9 volumes of methanol and 1 volume of chloroform, sonicate for 30 minutes and allow to stand for 90 minutes in a freezer. Immediately filter through a pledget of cotton, a solid phase extraction kit consisting of a hydrophilic-lipophilic balanced reversed-phase sorbent (Water® or equivalent is suitable) and a 0.45-μm polyvinylidene fluoride filter (Vertical® or equivalent is suitable.), successively, until a clear solution is obtained. Fold a filter paper into a quarter and open it partly to form a funnel, place a few drops of the solution into the centre of the paper and allow the filter paper to dry. Add a very small amount of a 1 per cent w/w mixture of Fast Blue B salt and anhydrous sodium sulfate and a few drops of a 10 per cent w/v solution of sodium bicarbonate: a purple red colour develops at the centre of the filter paper.
     (Note This colour is a combination of the colours of the different cannabinoids which are the major components of cannabis: tetrahydrocannabinol is red, cannabidiol is orange, and cannabinol is purple.)
     B. Carry out the test as described in the “Thin-Layer Chromatography” (Appendix 3.1).
     Standard solution A, Standard solution B, Standard solution C, Adsorbent, Mobile phase, Application, Development and drying, and Detection  Proceed as directed in the Identification under Cannabis Extract.
     Test solution Transfer 2 mL of the sample to a screw-capped, amber test-tube, add 8 mL of a mixture of 9 volumes of methanol and 1 volume of chloroform, sonicate for 30 minutes and allow to stand for 90 minutes in a freezer. Immediately filter
through a pledget of cotton, a solid phase extraction kit consisting of a hydrophilic-lipophilic balanced reversed-phase sorbent (Water® or equivalent is suitable) and a 0.45-μm polyvinylidene fluoride filter (Vertical® or equivalent is suitable.), successively, until a clear solution is obtained. Evaporate the filtrate to dryness under a fume hood. Dissolve the residue in 2.0 mL of methanol.
     Results As described in the Identification under Cannabis Extract.
     C. The chromatogram of the Assay preparation shows several peaks, one or two of which correspond to the tetrahydrocannabinol peak and the cannabidiol peak of the Standard preparations, as obtained in the Assay.

Microbial limit Comply with the requirements for Category 1A in the “Limits for Microbial Contamination” (Appendix 10.5).

Assay Carry out the determination as described in the “Liquid Chromatography” (Appendix 3.5).
     Diluent, Standard stock preparation A, Standard stock preparation B, Standard preparations, Internal standard preparation, System suitability preparation, Mobile phase A, Mobile phase B, Chromatographic system, System suitability,
Suitability requirements and Procedure  Proceed as directed in the Assay under Cannabis Extract.
     Assay preparation Transfer about 500 mg of Cannabis Sublingual Drops, accurately weighed, to a screw-capped amber test-tube, add 10 mL of a mixture of 9 volumes of methanol and 1 volume of chloroform, sonicate for 30 minutes and allow to
stand for 90 minutes in a freezer. Immediately filter through a pledget of cotton, a solid phase extraction kit consisting of a hydrophilic-lipophilic balanced reversed-phase sorbent (Water® or equivalent is suitable) and a 0.45-μm polyvinylidene fluoride filter (Vertical® or equivalent is suitable.), sucessively, until a clear solution is obtained. Evaporate 150.0 μL of the filtrate to dryness under a fume hood.  Dissolve the residue in 2.0 mL of Internal standard preparation, sonicate for 2 minutes and filter through a polyvinylidene fluoride membrane having a 0.45-μm porosity.
     (Note  In case the concentrations of tetrahydrocannabinol and cannabidiol in the Assay preparation are beyond the concentration ranges of standard curve, allow to adjust the volume of the filtrate taken for evaporation.)
     Calculation  By reference to the standard curve, calculate the contents of tetrahydrocannabinol (C₂₁H₃₀O₂) and cannabidiol (C₂₁H₃₀O₂) in a portion of the Sublingual Drops taken.

Other requirements  Comply with the requirements described under “Oromucosal Preparations” (Appendix 1.16).