Phenobarbital 10 mg/mL expressed as base, from sodium salt — oral solution · CGR-ES-086 (CGR-ES-086)

REFERENCE FORMULA

Reference formula

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

Ingredient	Source quantity	Scaled quantity
Phenobarbital sodium	1.09 g	—
Noncrystallising liquid sorbitol 70%	30 mL	—
Glycerol	10 g	—
Saccharin sodium	0.1 g	—
Preserved water without propylene glycol, CGR-ES-002 / FN/2017/EX/028	q.s. ad 100 mL	—
Sodium hydroxide 0.1 N, process aid only if required by pH	q.s. mL	—

Prerequisite formulations

CGR-ES-002 · Preserved water without propylene glycol AEMPS

Documentation

Preparation description

Clear, colourless, nonsterile oral solution. The 10 mg/mL strength is expressed as phenobarbital base; the source uses 1.09 g sodium salt per 100 mL. It contains sorbitol, glycerol, saccharin and parabens supplied by preserved water. ^[1]

Action and use

Barbiturate antiepileptic for individually prescribed treatment, principally generalised tonic-clonic or focal seizures. It is not intended for absence/myoclonic seizures, which may worsen [1,2]. Neonatal uses listed by the source require separate specialist approval and are not general indications of this sheet. ^{[1], [2]}

Specifications

Source requirements: clear colourless solution and pH 9.0–10.0 [1]. Nominal strength is 10 mg/mL as base. No numerical water activity or preservative-effectiveness result is supplied for the final alkaline solution. Paraben presence is not equivalent to demonstrated microbiological control [3]. ^{[1], [3]}

Light

Use amber glass and protection from light as specified by the source. Retain this protection during storage, transport and use; do not decant into a clear container for convenience. ^[1]

Air and oxidation

Keep tightly closed [1]. No quantitative oxygen/CO₂ study or nitrogen requirement is supplied. Limit opening and monitor the critical pH rather than assuming that alkalinity remains unchanged after air exposure. ^{[1], [5]}

Water and solubility

Use specifically propylene-glycol-free preserved water FN/2017/EX/028, not plain purified water as a substitution [1,3]. Its actual q.s. volume is recorded to calculate paraben content. Water activity has not been measured; sorbitol/glycerol presence is insufficient evidence for aw < 0.60. ^{[1], [3]}

Humidity

The finished preparation is liquid and no relative-humidity limit is given. For sodium-salt weighing, verify storage and CoA assay basis; do not correct quantity by an assumed moisture percentage. Weigh glycerol as 10 g regardless of changes in apparent fluidity. ^{[1], [5]}

Temperature

Store at 2–8 °C with the bottle closed and protected from light [1]. Prepare the preserved-water stock separately and use it after cooling and checking [3]. The final formula does not specify heating the phenobarbital solution; refrigeration does not justify using a cloudy or crystallised product. ^{[1], [3]}

pH and compatibility

pH 9.0–10.0 is required, measured with a calibrated meter. AEMPS permits adjustment with 0.1 N NaOH when necessary [1]. Add under controlled mixing, record the volume and recheck after homogenisation. No acidic back-titration agent is specified; do not improvise correction of an overshot batch. ^[1]

Other interactions

The source identifies incompatibility with acidic solutions [1]. Do not add juices or acidic flavours to the stock. A critical distinction is that the preserved-water monograph describes good paraben activity at pH 4–8 [3], while the final medicine requires pH 9–10. Do not arbitrarily lower pH to improve preservation. ^{[1], [3]}

Ingredient-specific information

The source uses 1 mg base≈1.09 mg sodium salt [1]; document the exact CoA assay basis. Measure 30 mL noncrystallising 70% sorbitol and weigh 10 g glycerol. Verify identity, traceability and DEG/EG controls for these liquid excipients following the relevant official recommendations [4]. The water stock contains 0.08 g methylparaben and 0.02 g propylparaben/100 mL [3]. ^{[1], [3], [4]}

Staff protection

Critical operations are weighing the barbiturate and handling 0.1 N NaOH. Control dust and use powder-free gloves, protective clothing and eye protection during pH adjustment/pouring. Exact glove compatibility and any extraction requirements follow the material SDSs. Closed API transfer and separate labelling of the alkaline process aid reduce exposure and mix-ups. ^{[1], [2], [5]}

Risk assessment

Clinical risks include sedation, respiratory compromise with other depressants, dependence/withdrawal seizures, serious skin reactions and enzyme induction with major interactions, including contraceptives [1,2]. Review porphyria, respiratory impairment, pregnancy and therapeutic monitoring. Sorbitol raises hereditary-fructose-intolerance/GI concerns; parabens may cause hypersensitivity [1]. Compounding risks are base-versus-sodium strength, pH, NaOH quantity, DEG/EG and unproven preservation at alkaline pH [3,4]. ^{[1], [2], [3], [4]}

Compounding conditions

For V mL: 0.0109×V g phenobarbital sodium,0.30×V mL 70% sorbitol,0.10×V g glycerol and 0.001×V g saccharin; vehicle to V mL. Label strength as 10 mg/mL base. Independently verify conversion and minimum weighable quantity. Account for and document NaOH volume in final-volume control without altering nominal concentration. ^{[1], [5]}

BUD rationale

AEMPS specifies 60 days at 2–8 °C protected from light and up to 30 days after opening [1]. This source-specific reference ceiling is selected only with documented local adoption of the exact formula, pH, glass container and controls. No independently retrieved full study verifies this exact formula/container, and no final-product aw/AET result is available. Final pH 9–10 is outside the vehicle’s stated good paraben-activity range 4–8 [3]; the product is therefore not automatically designated “validated preserved” or assigned the general 35-day category. Without local support for the specific period, the official conservative general aqueous-oral fallback is up to 14 days at 2–8 °C [5]. Final expiry=min(preparation+60 days, opening+30 days, any earlier applicable component/vehicle expiry). No Greek legal limit or USP validation is implied. ^{[1], [3], [5]}

Prerequisites

CGR-ES-002 / FN/2017/EX/028: preserved water without propylene glycol. Before use, verify the 0.08/0.02 g per 100 mL paraben composition, clarity, batch and current expiry. Do not use another preserved-water composition or preserved syrup. Separately prepare or procure verified 0.1 N NaOH. ^{[1], [3]}

Equipment

Balance for API/glycerol/saccharin, suitable measurement of 30 mL viscous sorbitol, vessel/stirrer and final-volume apparatus. Use a pH meter calibrated across the alkaline range, controlled NaOH dispensing equipment and amber bottle with oral syringe. Avoid acidic residues in equipment. ^{[1], [3], [5]}

Compounding method

1. Weigh/measure and independently verify base-equivalent strength. 2. Dissolve the sodium salt completely with mixing in 50 mL preserved water. 3. Add glycerol and saccharin, followed by sorbitol. 4. Make to final volume with the same vehicle and homogenise. 5. Check pH 9–10; if needed, add 0.1 N NaOH in a controlled manner, record and recheck pH/final volume. 6. Package clear product in screw-capped amber glass and refrigerate. ^{[1], [5]}

Observations

This is not the same as 10 mg/mL phenobarbital sodium solution. Here 1 mL nominally represents 10 mg base from 10.9 mg sodium salt. The source states approximately 270 mg sorbitol/mL; verify this from the actual assay/density of the noncrystallising 70% material, not an assumption of 70% w/v. Changing vehicle/sweetener requires reassessment. ^[1]

Container and packaging

Use screw-capped amber glass as specified, with a tight closure suitable for the alkaline vehicle. Provide an oral-syringe adaptor, tamper evidence and an opening-date entry. Switching to plastic is not covered by this source’s data. ^{[1], [5]}

Quality control

Check sodium-salt identity/assay and correct base expression, weights and final volume. Accept only clear colourless product with measured pH 9–10 [1]. Record actual vehicle/NaOH quantities. Support for the specific BUD requires an approved assay/microbiological control plan; clarity and parabens do not demonstrate potency or AET. Apply DEG/EG excipient controls under the quality plan [4,5]. ^{[1], [4], [5]}

Storage

Store at 2–8 °C, protected from light and tightly closed. After opening, no more than 30 days and always within the final expiry. Maintain secure access. Turbidity, crystals or changed appearance require quarantine and assessment; do not shake and administer it as a suspension. ^[1]

Dispensing

Clarify “10 mg/mL expressed as phenobarbital base” with prescriber and caregiver. State dose in mg and mL and provide an oral syringe. Review concurrent medicines, pregnancy and sorbitol/paraben suitability. Do not stop treatment abruptly; rash/mucosal lesions or severe sedation require immediate medical assessment. Record first opening on the bottle. ^{[1], [2]}

Labelling

Phenobarbital 10 mg/mL expressed as base — ORAL SOLUTION from sodium salt. Contains sorbitol [verified amount: __ mg/mL], methylparaben and propylparaben. Patient: __. Dose: __ mg base = __ mL, frequency: __. Oral use only. Refrigerate 2–8 °C, protect from light. Batch: __. Prepared: __. Opened: __. Use by: __ [earliest applicable date]. Keep out of children’s reach. compounding.gr. ^{[1], [3]}

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: FENOBARBITAL 10 MG/ML SOLUCIÓN ORALFN/2021/FMT/031; 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 — Gardenal 50 mg comprimidos, SmPCCurrent CIMA version retrieved 2026-10-13Sections 4.3–4.9Phenobarbital clinical hazards only; tablet excipients, tablet dose and shelf life do not transfer2026-10-13
AEMPS — FN/2017/EX/028 Agua conservante sin propilenglicolCurrent standalone AEMPS PDF; retrieved 2026-10-13PDF p.2, composition and observationsExact preservative-water dependency; paraben amounts and documented pH activity range, not final-product AET2026-10-14
FDA — Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene GlycolMay 2023 Revision 1SectionsI andIV; recommendations covering pharmacy compoundersSpecific glycerol/noncrystallising sorbitol quality and supply-chain risk; US recommendations, not Greek statutory requirements2026-10-13
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