REFERENCE FORMULA
Reference formula
Reference basis: 100 mL τελικού σιροπιού / 100 mL final syrup
| Ingredient | Source quantity | Scaled quantity |
|---|---|---|
| Chloral hydrate, pharmacopoeial quality | 10 g | — |
| Purified water | 5 mL | — |
| Strawberry flavour suitable for pharmaceutical use | q.s. — | — |
| Preserved simple syrup — FN/2019/EX/029 (CGR-ES-003) | q.s. ad 100 mL | — |
Prerequisite formulations
Documentation
Preparation description
Clear, colourless oral solution containing 100 mg chloral hydrate per mL in a preserved sucrose vehicle with strawberry flavour. This sheet covers the preserved formulation only. The 10% concentration is w/v, not w/w. [1]
Action and use
The source describes sedation before painless paediatric diagnostic procedures and mentions critically ill patients; the drug does not provide analgesia [1]. Suitability is determined by a specialist in a monitored setting. The UK authorisation of oral products for restricted insomnia treatment is not a general authorisation for paediatric procedural sedation [2]. [1], [2]
Specifications
Theoretical content is 10 g/100 mL = 100 mg/mL. AEMPS requires a clear, colourless solution with pH 4.0–5.0. It gives no numerical viscosity, density or assay limit for the finished medicated syrup. The density specification of CGR-ES-003 is not a specification for this finished medicine. Final volume determines strength. [1], [5]
Light
Limit unnecessary light exposure during preparation and handling. Store in amber glass; light protection is a condition of the source 90-/30-day periods. No quantitative photostability exposure limit is specified. [1]
Air and oxidation
Keep the bottle tightly closed and avoid prolonged exposure during transfers. Water loss changes both drug concentration and syrup composition. Do not assess odour by directly inhaling the preparation. The source requires no nitrogen or other inert gas. [1]
Water and solubility
The 5 mL purified water is the specified initial dissolution component; final volume is made up with preserved syrup. Do not replace syrup with water to ease mixing. Finished-formula water activity has not been established; substantial sucrose content alone does not justify a low-aw classification. [1], [5]
Humidity
Weigh hygroscopic chloral hydrate with minimal exposure and promptly reclose its container. This monograph refers to the usual syrup-preparation conditions and gives no additional numerical relative-humidity limit. Record actual laboratory conditions. [1]
Temperature
Store the final syrup below 25 °C. The active-drug dissolution method does not specify heating. Heat used to prepare CGR-ES-003 belongs to the separate vehicle process; the vehicle must be suitable for incorporation and final-volume measurement at the working temperature. Do not extend dating by arbitrarily refrigerating the product. [1], [5]
pH and compatibility
Measure pH after final homogenisation: required range 4.0–5.0. Use a calibrated pH meter and document temperature/method. The source calls for adjustment if necessary but identifies no adjusting agent or concentration. Hold an out-of-range batch until a preapproved, documented procedure is available; do not improvise addition of acid or base. [1]
Other interactions
Ingredient-specific information
CGR-ES-003 supplies sucrose and methyl-/propylparaben [5]. The source estimates approximately 0.71 g sucrose per mL of finished medicine and flags diabetes, disorders of sugar metabolism/absorption, dental caries and possible delayed paraben allergy [1]. Check the actual flavour specification for additional solvents/allergens. Record the amount used; q.s. does not permit undocumented product substitution. [1], [5]
Staff protection
During weighing use local extraction, gloves and eye protection; avoid dust. ICSC records toxicity and carcinogenic/genotoxic hazards. Minimise exposure and apply the actual raw-material SDS [3]. [3]
Risk assessment
Priority risks are strength and mg/mL verification: prescribed D mg corresponds to D/100 mL, not the twice-larger volume of the 50 mg/mL rectal preparation. Independently check dose, route, patient and measuring device. Respiratory depression and arrhythmia require supervised administration [1]. Current oral SmPC flags QT, hypokalaemia, bradyarrhythmia and acute porphyria; review other sedatives/QT-prolonging agents and coumarins [4]. Hepatic/renal disease, severe cardiac disease and gastroduodenal disease require specific assessment. [1], [4]
Compounding conditions
Before execution verify CGR-ES-003 identity and expiry, flavour suitability and approved batch size. For V mL, use 0.10×V g chloral hydrate and 0.05×V mL purified water; syrup makes up the final volume. Do not equate vehicle mass and volume. Actual lots, quantities, times, results and signatures are entered during real preparation. [1], [5]
BUD rationale
AEMPS gives 90 days unopened and 30 days after opening, below 25 °C and protected from light [1]. Here these are reference ceilings: 90 days from preparation and, after opening, no more than 30 days, always within the original expiry, subject to earlier ingredient/vehicle expiry or local restriction. Exact composition, pH 4–5, approved CGR-ES-003, amber glass and documented controls are prerequisites. Bustos-Fierro studied 7% syrup with different vehicle/flavour; its 180-day findings do not transfer [6]. No matched study, final aw or AET was found for this formula. This is neither USP validation nor a Greek legal rule. The neonatal unpreserved variation is excluded from this dating. [1], [5], [6]
Prerequisites
Vehicle: CGR-ES-003 / FN/2019/EX/029, preserved simple syrup. Confirm the current register ID and approved methyl-/propylparaben vehicle recipe. AEMPS mentions a neonatal modification without flavour or preservatives; that is a different formulation requiring separate assessment and documentation. Vehicle dating does not automatically transfer to the medicated mixture. [1], [5]
Equipment
Use a suitable accurate balance, closable weighing vessel, volumetric devices for 5 and 100 mL, beakers, stirring equipment suitable for viscous syrup, calibrated pH meter, thermometer and amber glass screw-cap bottle. For administration provide an appropriately graduated oral syringe and independently verify dose volume. [1], [4]
Compounding method
1. Weigh 10 g chloral hydrate. Measure 5 mL purified water into a 100 mL beaker. Add the drug and stir until fully dissolved.
2. Add 50 mL preserved simple syrup CGR-ES-003 and the documented quantity of strawberry flavour; mix uniformly.
3. Transfer into a 100 mL graduated cylinder and make up to 100 mL with the same vehicle. Transfer to a beaker and homogenise.
4. Measure pH; accept 4.0–5.0. If outside range, use only a preapproved documented adjustment procedure and recheck final volume/pH.
5. Check the solution and pack in amber glass with screw cap. [1]
2. Add 50 mL preserved simple syrup CGR-ES-003 and the documented quantity of strawberry flavour; mix uniformly.
3. Transfer into a 100 mL graduated cylinder and make up to 100 mL with the same vehicle. Transfer to a beaker and homogenise.
4. Measure pH; accept 4.0–5.0. If outside range, use only a preapproved documented adjustment procedure and recheck final volume/pH.
5. Check the solution and pack in amber glass with screw cap. [1]
Observations
The 100 mg/mL syrup and 50 mg/mL enema are distinct formulas and are not interchangeable by route or dose volume. Do not adopt shelf-life or excipient warnings from a differently formulated commercial medicine; the UK product contains different excipients [4]. AEMPS comments on Spanish psychotropic controls do not establish Greek requirements. AEMPS describes neonatal use, whereas MHRA highlights prolonged metabolite elimination in neonates/infants and the UK licensed oral product is not for children under 2 years [2,4]. This difference requires a specialist clinical decision, not automatic transfer of indications. [1], [2], [4]
Container and packaging
Use amber glass with a securely closing screw cap and suitable capacity for the final volume without overfilling. Record first-opening date. The 90-/30-day periods are not established for storage in prefilled plastic syringes; the oral syringe is a measuring device used at administration. [1]
Quality control
Independently check raw-material identity, 100 mg/mL strength, amounts and final volume. Verify complete dissolution, clarity, lack of colour/visible particles, pH 4.0–5.0, correct vehicle/flavour and closure. Confirm CGR-ES-003 batch documents, dates and oral labelling. Additional assay/microbial testing requires methods suitable for this vehicle. This literature-based work includes no batch test results. [1], [5]
Storage
Store below 25 °C, tightly closed and protected from light. Record preparation, first opening and final discard dates; the earliest limit always governs. The in-use period does not restart the original shelf-life. Keep in a controlled area, away from children and segregated from rectal/injectable preparations. [1]
Dispensing
Supply on specialist order with both mg and mL stated, for oral use in a supervised clinical setting. Review allergy, sucrose/parabens and flavour composition. If directed by the clinical team, a measured dose may be given with a suitable small amount of liquid for palatability; this concerns immediate administration, not dilution of stored stock. Ensure the entire measured dose is administered. Pregnancy/breastfeeding requires specific reassessment: the current UK oral SmPC says not to use, more restrictively than some wording in the older AEMPS source [4]. [1], [4]
Labelling
CHLORAL HYDRATE 100 mg/mL — ORAL SYRUP. FOR ORAL USE ONLY. Volume: ___ mL. Patient/order: ___ mg = ___ mL. Contains sucrose (approximately 0.71 g/mL according to source) and methyl-/propylparaben. Batch: ___. Prepared: ___. Use by: ___. First opened: ___. Discard after opening: ___, always before original expiry. Store below 25 °C, tightly closed and protected from light. Administer only with clinical monitoring. Keep out of reach of children. [1]
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, FN/2003/FMT/039: Hidrato de cloral, jarabeModificado 2022PDF pp.2–6; §§3–12 and patient leafletExact 10% preserved master formula; pH 4–5; amber glass; 90-day closed and 30-day in-use periods; neonatal vehicle variation requires separate assessment2026-10-14
- MHRA — Chloral hydrate, cloral betaine (Welldorm): restriction of paediatric indication6 October 2021Advice for healthcare professionals; Off-label use for sedation in childrenCurrent clinical context; prolonged metabolite half-life in infants. UK oral-product authorisation is not a rectal authorisation.2026-10-13
- ILO/WHO — International Chemical Safety Card 0234: Chloral hydrateApril 2013 card; accessed 2026Prevention; Chemical dangers; Exposure and health effectsOccupational handling of chloral hydrate CAS 302-17-0; raw-material hazards, not a finished-mixture CLP classification.2026-10-13
- Marlborough Pharmaceuticals — Chloral Hydrate 500 mg/5 mL Oral Solution, SmPCSmPC revised 17 August 2026; emc update 24 August 2026Sections 4.1–4.6, 4.8, 5.2Authorised oral-product safety. Its excipients, dosing and shelf-life are not substituted for this compounded formulation.2026-10-13
- AEMPS — Formulario Nacional, FN/2019/EX/029: Jarabe simple (84% P/V) con conservante2019 monograph, public standalone PDFPDF p.2; §§3–8Dependency CGR-ES-003: sucrose vehicle with methyl- and propylparaben. Its characteristics and period do not independently validate the finished medicated syrup.2026-10-14
- Bustos-Fierro C et al. Stability evaluation of 7% chloral hydrate syrup contained in mono and multi-dose bottles under room and refrigeration conditions. Farm Hosp. 2013;37: 4–92013; DOI 10.7399/FH.2013.37.1.96Full text pp.4–9; Materials and Methods, Tables 1–2 and AppendixPrimary 7% syrup study with different vehicle/flavour/pH; not a matched study for the AEMPS 10% preserved strawberry formula.2026-10-13
- 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