Tretinoin 0.025% gel · TECH-ES-TRET-001 (TECH-ES-TRET-001)

REFERENCE FORMULA

Reference formula

Reference basis: 100 g finished gel;0.25 mg/g

Ingredient	Source quantity	Scaled quantity
Tretinoin	25 mg	—
Butylhydroxytoluene(BHT)	20 mg	—
Neutral hydroalcoholic gel EX021	q.s. ad 100 g	—

Prerequisite formulations

CGR-ES-056 · Neutral hydroalcoholic carbomer gel EX021

Documentation

Preparation description

Firm opaque yellowish gel containing tretinoin 0.25 mg/g and BHT 0.2 mg/g. FN describes the finished product as opaque, unlike the clear unmedicated base. ^[1]

Action and use

Cutaneous treatment of comedonal acne; FN also describes adjunctive use for photoageing. Use only within a defined treatment plan. EMA contraindicates topical retinoids during pregnancy and when planning pregnancy. ^{[1], [3]}

Specifications

Firm opaque yellowish gel without grittiness/separation;25 mg tretinoin per 100 g. pH 6–6.5 is the EX021 base specification, not a published finished-active stability study. ^{[1], [2]}

Light

Protect during handling/storage; the FN final leaflet requires light protection. Aluminium tube limits exposure. Increased colour intensity warrants rejection/investigation as indicated by the source. ^[1]

Air and oxidation

Work promptly with vessels covered where practicable and avoid aeration. BHT is part of this formula; its presence does not establish tolerance of uncontrolled air exposure or longer dating. ^[1]

Water and solubility

Base contains preserved water and is not anhydrous. Do not add extra water to dilute the active. Preserve the EX021 internal preservative system. ^{[1], [2], [6]}

Humidity

Specific manufacturing condition: relative humidity ≤ 60%. Protect from moisture during storage and keep the tube closed. ^[1]

Temperature

Manufacture/store below 25 °C. Do not introduce heat to accelerate dissolution without a supported revision; no tretinoin heating step is specified. ^[1]

pH and compatibility

EX021 is gelled with trolamine to pH 6–6.5. Record pH after active incorporation without treating it as proof of chemical stability. Altered pH/carbomer requires reassessment. ^{[1], [2]}

Other interactions

Additional keratolytics, depilatories, exfoliants or strongly alcoholic products can increase irritation. Do not incorporate another active without compatibility evidence. ^[1]

Ingredient-specific information

Tretinoin is all-trans retinoic acid, not isotretinoin. Exact EX021 uses carbomer 940 at 1%, ethanol 96%10 g/100 g, propylene glycol 5% and preserved water, with trolamine to pH 6–6.5. This sheet does not adopt the generic base’s optional increase of alcohol to 25%. ^{[1], [2]}

Staff protection

Weigh 25 mg active using a suitable balance minimum weight and powder containment. Gloves, coat, eye protection and careful cleaning limit inadvertent retinoid exposure. Control vapour/ignition hazards when handling ethanol. ^{[1], [3], [4]}

Risk assessment

Decimal check is essential: 25 mg/100 g=0.025%, not 0.25%. Clinically assess pregnancy/plans without automatically transferring oral-isotretinoin programme requirements. Additional risks are UV exposure, irritation and product photochemical deterioration. ^{[1], [3]}

Compounding conditions

First confirm the balance can accurately weigh 25 mg tretinoin and 20 mg BHT; otherwise use a validated pre-dilution or larger batch. Maintain below 25 °C, RH ≤ 60%, controlled light and prompt handling. ^[1]

BUD rationale

AEMPS reports 1 month below 25 °C, protected from moisture and light in an aluminium tube. The source reference ceiling is 28 days and no later than 1 calendar month. It is not an assigned operational BUD for this technical record: the sequence conflict between FMT021 and EX021 must first be resolved and approved. No independently matched vehicle/tube stability study or final water-activity/AET result was retrieved. The unmedicated base’s 6 months do not transfer. No preparation, laboratory validation or final release is claimed. [1,2] The 28-day value is only the conservative editorial conversion of one calendar month; it is not a completed local BUD. ^{[1], [2]}

Prerequisites

Neutral hydroalcoholic gel EX021 → CGR-ES-056; preserved water EX001 → CGR-ES-018. Preserve the specified dependent-base composition, but clarify the alcohol-phase addition sequence before manufacture. Do not add unplanned extra ethanol. ^{[1], [2], [6]}

Equipment

Suitable analytical balance, light-protected vessels,500-sieve for base where used, gentle mixer, pH meter, thermometer/hygrometer and tube-filling equipment. ^{[1], [2]}

Compounding method

Technical reference, not an executable reconciled method. FMT021 directs preparation of EX021 and dissolution of 25 mg tretinoin plus 20 mg BHT in its ethanol at the final gel-manufacturing step. However, EX021 adds ethanol with carbomer, propylene glycol and preserved water before a 24-hour rest, followed by trolamine neutralisation to pH 6–6.5. These instructions leave the alcohol-addition sequence unresolved. Before manufacture, obtain an authorised clarification or validate and approve one explicit sequence, including light protection, hydration, neutralisation and final mass. Do not use extra ethanol or imply that an assumed order has been verified. [1,2] ^{[1], [2]}

Observations

The FMT021 and EX021 alcohol-addition instructions are not mutually consistent. This record belongs in the technical research appendix until one process is clarified, documented and approved. The listed formula is retained; no alternative manufacturing order has been invented. ^{[1], [2]}

Container and packaging

Use an aluminium tube suitable for the hydroalcoholic base, effectively sealed with qualified internal compatibility. Provide opaque outer protection where needed during supply. ^[1]

Quality control

Independently verify 25 mg/20 mg, final mass, colour/uniformity, absence of crystals, pH record and closure. Colour monitoring does not replace a stability-indicating tretinoin/isomer assay. ^{[1], [2]}

Storage

Keep tube closed below 25 °C, protected from light/moisture. Discard for marked colour intensification or altered consistency. ^[1]

Dispensing

Apply only to clean, fully dry skin as prescribed. Avoid UV/sunlamps and use sun protection. Avoid eyes, mucosa, eczematous or sunburnt skin. Do not use during pregnancy/planning pregnancy. The source professional section also contraindicates use during breastfeeding and with a history of epithelioma; retain these restrictions pending specific clinical reassessment. This technical record is not ready for dispensing. ^{[1], [3]}

Labelling

RESEARCH LABEL OUTLINE — NOT FOR DISPENSING before process approval and BUD assignment. Tretinoin 0.025% (0.25 mg/g) · FOR SKIN USE. Do not use during pregnancy/planning pregnancy. Directions: __. Use sun protection during treatment. Store below 25 °C, away from light, moisture and children. Batch: __. Prepared: __. Use by [only after approved assignment]: __. ^{[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 — FN/2003/FMT/021 TRETINOÍNA, GEL DECurrent AEMPS standalone PDF; code FN/2003/FMT/021PDF p 2 §§3–7; subsequent safety and patient informationExact formulation, process, source shelf life and formulation-specific precautions; independent factual compilation, not official translation.2026-10-14
AEMPS — Formulario Nacional — FN/2003/EX/021 GEL NEUTRO HIDROALCOHOLICOCurrent AEMPS standalone PDF; code FN/2003/EX/021PDF p 2 §§3–7; subsequent safety and patient informationExact formulation, process, source shelf life and formulation-specific precautions; independent factual compilation, not official translation.2026-10-14
EMA — Retinoid-containing medicinal products, Article 31 referralEC decision 21 June 2018; retrieved 13 October 2026Information for healthcare professionals: topical retinoids and pregnancyCurrent precautionary contraindication in pregnancy/planning pregnancy; no transfer of the oral retinoid pregnancy-prevention programme to a topical formulation.2026-10-13
CDC/NIOSH Pocket Guide — Ethyl alcoholPage reviewed 30 October 2019; retrieved 13 October 2026Flammability, incompatibilities and personal protectionEthanol raw-material handling; not a measured flash point or hazard classification of the finished mixture.2026-10-13
USP — Compounding Standards and Beyond-Use DatesNovember 2022 USP publication, public copy hosted by Mississippi Boardp 2 nonsterile comparison tableGeneral category limits only; not product-specific stability, antimicrobial effectiveness or Greek law.2026-10-13
AEMPS — Formulario Nacional — FN/2003/EX/001 AGUA CONSERVANTECurrent AEMPS standalone PDF; code FN/2003/EX/001PDF p 2 §§3–7; subsequent safety and patient informationExact formulation, process, source shelf life and formulation-specific precautions; independent factual compilation, not official translation.2026-10-14
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