Methadone hydrochloride 10 mg/mL (1% w/v) aqueous oral solution · CGR-ES-083 (CGR-ES-083)

REFERENCE FORMULA

Reference formula

Reference basis: 100 mL τελικού διαλύματος / 100 mL final solution

Ingredient	Source quantity	Scaled quantity
Methadone hydrochloride, pharmacopoeial grade	1 g	—
Purified water	q.s. ad 100 mL	—

Prerequisite formulations

No separate prerequisite monograph is listed.

Documentation

Preparation description

Nonsterile aqueous solution containing 1 g methadone hydrochloride in a final 100 mL: 10 mg/mL of the stated salt. The source describes a clear, colourless to slightly yellow liquid. No syrup, preservative or pH-adjusting ingredient is included. ^[1]

Action and use

Opioid for individually prescribed, medically supervised treatment, particularly an authorised opioid-dependence programme; severe pain is also listed by the formulary [1]. Indication, opioid tolerance and monitoring must be established before supply [2]. This sheet does not prescribe a general dosing regimen. ^{[1], [2]}

Specifications

Source specifications are clarity, colourless to slightly yellow appearance and pH ≤ 6.5 [1]. Nominal strength is 10 mg/mL. Assay, microbiological limits and container suitability require an approved local control plan; no measurements are claimed here. A study recovery criterion is not automatically a batch-release specification [3,4]. ^{[1], [3], [4]}

Light

Use amber glass or suitable opaque plastic as specified by the source [1]. Amber glass is selected when using the study as corroboration [3]. The study does not establish storage in a transparent light-exposed bottle. ^{[1], [3]}

Air and oxidation

Prompt reclosing limits contamination and volume change [4]. The study included brief daily opening of specified glass bottles, not repeated patient dilution or decanting [3]. No oxygen threshold or inert-gas requirement is established. ^{[3], [4]}

Water and solubility

Purified water is the sole vehicle. Use controlled pharmacopoeial-quality water, not tap water. With no preservative, hygienic preparation and avoidance of returning unused doses to the bottle are essential. Water activity has not been measured for the present product. ^{[1], [4]}

Humidity

No special relative-humidity limit is specified for the finished liquid. During weighing, keep the raw-material container closed except while needed and follow the conditions for its actual batch. Humidity is not a basis for an invented mass correction. ^{[1], [4]}

Temperature

AEMPS requires refrigeration; the operating target here is 2–8 °C. M 1 was studied at 5±3 °C, 25±2 °C and 40±2 °C [3], but this sheet retains the formulary refrigeration requirement. Heating to accelerate dissolution is not introduced without a validated change. ^{[1], [3]}

pH and compatibility

Measure with a calibrated pH meter and record the result: acceptance pH ≤ 6.5 [1]. The study reports approximately 6.5–7, differing from the AEMPS limit [3]; it does not justify relaxing that limit. Investigate an out-of-specification batch; the source supplies no approved titrant or adjustment procedure. ^{[1], [3]}

Other interactions

Do not mix the stock with juices, flavourings or other medicines. Such changes alter pH, composition and the stability evidence. Oxidative and alkaline stress were particularly destabilising in the study [3]; forced-degradation findings are not instructions to add an antioxidant. ^{[1], [3]}

Ingredient-specific information

Raw material is methadone hydrochloride corresponding to RFE 0408, not free base or a different-strength commercial solution [1]. Verify identity, assay basis and traceability before weighing. The formula remains 10 mg/mL hydrochloride salt; Eptadone excipients are not components of this preparation [2]. ^{[1], [2], [4]}

Staff protection

Weighing 1 g of a potent opioid is the critical exposure operation. Apply a local dust-containment plan, closed transfers, powder-free gloves, protective clothing and splash eye protection. Respiratory protection/extraction is selected from the exact raw-material SDS and exposure assessment. Do not taste-test the preparation [2,4]. ^{[2], [4]}

Risk assessment

Critical events include confusing 1% with 1 mg/mL, a dose decimal error, child access, powder exposure and cross-contamination. Methadone can cause respiratory depression and accumulation; other depressants and QT-prolonging factors increase risk [2]. Independently check concentration, mg-to-mL conversion, device and patient identity; maintain secure inventory accountability under applicable law [4]. ^{[2], [4]}

Compounding conditions

For final volume V mL, use 0.010×V g methadone hydrochloride on the specified assay basis and water to V mL. Check the balance minimum weighable quantity. Independently verify the calculation before dissolution; do not add a precautionary excess for “losses”. Prepare cleaned equipment, a segregated work surface and an approved batch record. ^{[1], [4]}

BUD rationale

AEMPS specifies 30 days refrigerated [1]. Direct M 1 research using the same composition found physicochemical and microbiological stability for 91 days in previously sterilized amber glass, closed or briefly opened daily, at 5±3/25±2/40±2 °C; preservative effectiveness was tested only for the different M 2 formulation [3]. The pH and process differences prevent automatic transfer of 91 days. The selected reference ceiling is 30 days from preparation at 2–8 °C, conditional on documented local adoption of the exact composition, container and controls. It is neither a Greek statutory limit nor automatic USP validation. If the local process does not support the specific period, the official general aqueous-oral fallback is up to 14 days at 2–8 °C [4]. Earlier component expiry or supply restrictions prevail. ^{[1], [3], [4]}

Prerequisites

No composite vehicle or dependent base is used. Approved procedures are needed for weighing, oral solutions, controlled-medicine handling, cleaning and labelling. AEMPS PN codes identify source procedures and do not replace locally approved SOPs. ^{[1], [4]}

Equipment

Suitable balance, dust-controlled weighing accessories, glass dissolving vessel, stirrer, suitable final-volume measuring apparatus, calibrated pH meter and bottle with an oral-syringe adaptor. Choose syringe size for the individual dose volume, not the bottle capacity. ^{[1], [4]}

Compounding method

1. Identify the raw material, independently check the calculation and weigh. 2. Dissolve methadone hydrochloride in part of the purified water until fully clear. 3. Transfer quantitatively and make to a final 100 mL with water; mix. 4. Check appearance and pH ≤ 6.5. 5. Package, close, label and refrigerate promptly. This composition does not specify addition of a pH modifier. ^{[1], [4]}

Observations

1 g/100 mL equals 10 mg/mL, not 1 mg/mL. For a prescribed D mg amount of the same salt, volume is D/10 mL. This calculation is neither dose selection nor an opioid-conversion rule. Dilution of a dose, if directed by the prescriber, does not extend the original bottle BUD. ^{[1], [2]}

Container and packaging

Prefer an amber-glass bottle with tight closure, tamper evidence and suitable adaptor. Use a child-resistant closure where permitted and usable by the patient. AEMPS also permits opaque plastic, but the glass-container study does not establish its performance. ^{[1], [3], [4]}

Quality control

Independently check identity/weighing, final volume, uniformity and pH; inspect particles and colour. The study supplies a stability-indicating HPLC method and microbiological protocol [3], requiring local method suitability before use. No laboratory pass is claimed without actual results. ^{[1], [3], [4]}

Storage

Store at 2–8 °C, tightly closed and protected from light, with restricted access. Assess temperature excursions from their recorded magnitude, duration and batch circumstances; the experimental 40 °C result is not an automatic excursion allowance. Do not use if particles, turbidity or an unexpected colour change appear. ^{[1], [3], [4]}

Dispensing

Supply only after legal and clinical verification of the individual prescription/programme. Label mg/mL and the prescribed dose in both mg and mL; demonstrate the oral syringe. No injection or sharing. Counsel on secure storage, additional depressants and urgent assessment for excessive drowsiness or slow breathing. ^{[1], [2], [4]}

Labelling

Methadone hydrochloride 10 mg/mL — ORAL SOLUTION. Patient: __. Dose: __ mg = __ mL, frequency: __ as prescribed. Oral use only. Store at 2–8 °C, protected from light, tightly closed and out of children’s reach. Batch: __. Prepared: __. Use by: __ [documented BUD]. Quantity: __. compounding.gr. ^{[1], [2], [4]}

v9_controls

The numeric value is a literature reference ceiling subject to its specific conditions. No actual batch BUD has been assigned and no aw measurements have been produced. The exact formula, prerequisites, container, storage and quality evidence require approval for the actual application. The BUD clock starts when compounding begins. Use the shortest applicable supported limit and assess in-use dating separately. USP categories are a technical framework and are not presented as Greek legislation.

Sources and references

AEMPS — Formulario Nacional: HIDROCLORURO DE METADONA, SOLUCIÓN AL 1% DEFN/2003/FMT/011; current standalone PDF retrieved 2026-10-13PDF p. 2, sections 3–7; subsequent clinical and patient sectionsExact master formula, preparation, source specifications, container and source-specific period; independently adapted, not an official translation2026-10-14
AEMPS CIMA — Eptadone 5 mg/mL solución oral, SmPCCurrent CIMA version retrieved 2026-10-13Sections 4.1–4.9Current oral-methadone pharmacological hazards only; different strength/excipients; no formulation or BUD transfer2026-10-13
Álvaro-Alonso EA et al. — Physicochemical and Microbiological Stability of Two Oral Solutions of Methadone Hydrochloride 10 mg/mLMolecules 2022;27: 2812. DOI 10.3390/molecules 27092812; full textTable 1, sections 2.2–2.4 and 3; M 1 onlyMatching API/strength/water composition; previously sterilized amber-glass containers; 91-day study; pH and process differences prevent unconditional extension2026-10-14
Ministerio de Sanidad — Guía de buenas prácticas de preparación de medicamentos en servicios de farmacia hospitalariaJune 2014; official AEMPS copyAnnexes 3–4, PDF pp. 51–58; especially pp. 54–57Risk-based controls, nonsterile preparation, packaging, independent checks and conservative fallback; Spanish hospital guidance, not Greek legislation2026-10-13
USP — General Chapter <795> Frequently Asked QuestionsNovember 1, 2023 FAQ; rechecked 14 October 2026Questions 52, 54–56, 61, 64–66General category/extension rules only; not exact-product stability evidence.2026-10-14