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Packaging materials · Glass containers for pharmaceutical use (vials, ampoules, bottles)

Hydrolytic Resistance of Glass Containers (Surface Glass Test)

Measures how much alkali the inner surface of a glass container releases into water under autoclave conditions. The containers are filled with water, autoclaved at 121 °C, and the water is titrated with 0.01 M hydrochloric acid. The result classifies the container and confirms it meets its glass type.

  • Autoclave extraction followed by acid–base titration with 0.01 M HCl
  • Autoclave
  • Burette & glassware
  • Analytical balance

Reference: Typical procedure based on USP <660> and Ph. Eur. 3.2.1. Filling volumes, autoclave cycle details and limits depend on container size and glass type; see the current chapter.

PRINCIPLE

Why this method works

When glass is in contact with hot water, alkali ions (mainly sodium) leach from the surface and make the water slightly alkaline. Autoclaving speeds this up in a controlled way. Titrating the extract with dilute acid to a methyl red endpoint measures the alkali released. Type I borosilicate glass releases very little; Type II (surface-treated soda-lime) has a treated inner surface that releases little; Type III soda-lime glass releases more. The surface glass test checks the inner surface as the container will be used.

Instruments used

MATERIALS

Reagents & standards

ReagentGrade / specification
Hydrochloric acid0.01 M volumetric solution (titrant)
Methyl red solutionIndicator
Purified waterFreshly boiled and cooled or otherwise CO₂-free, of suitable quality (as specified in the chapter)
SAMPLE PREPARATION

Preparing the sample

  1. 01

    Brimful capacity

    Determine the brimful capacity of a few containers by weighing water.

  2. 02

    Rinse

    Rinse containers with purified water as specified.

  3. 03

    Fill

    Fill to 90% of brimful capacity with purified water.

  4. 04

    Autoclave

    Cover and autoclave to 121 °C and hold for 60 minutes.

  5. 05

    Cool

    Cool and pool the extract as specified.

  6. 06

    Titrate

    Titrate an aliquot with 0.01 M HCl to methyl red endpoint.

Procedure

  1. 1Take the number of containers stated in the chapter. Determine the average brimful capacity of the type by filling with water and weighing.
  2. 2Rinse each container with purified water, then fill with purified water to 90% of its brimful capacity.
  3. 3Cover the containers loosely (for example with inert foil or a watch glass) and place them in the autoclave.
  4. 4Autoclave following the chapter's cycle: heat to 100 °C and vent steam, raise to 121 °C, hold for 60 minutes, then cool to 100 °C and remove (rates and times as specified).
  5. 5Cool the containers in water and combine the liquid from the containers as specified.
  6. 6Transfer the stated aliquot to a conical flask, add methyl red, and titrate with 0.01 M HCl to the endpoint.
  7. 7Perform a blank titration on the same volume of purified water.

Standard preparation

  1. 1Standardise or check the factor of 0.01 M HCl as required by your SOP; use a burette suitable for small volumes (for example a 10 mL Class A burette or microburette).

Notes for analysts

  • Type I: borosilicate glass with high hydrolytic resistance, for most parenterals. Type II: soda-lime glass with a treated inner surface. Type III: soda-lime glass with moderate resistance, for non-parenteral products or some powders.
  • The surface test measures the container as used. The glass grains test measures the bulk glass. The surface etching test (with hydrofluoric acid) shows whether high resistance comes from surface treatment.
  • Use CO₂-free water and titrate soon after cooling: carbon dioxide affects small acid–base titrations.
  • Small titration volumes need a microburette or a burette with fine graduations.
TEST CONDITIONS

Method parameters (typical)

Filling volume90% of brimful capacity
Autoclave121 °C held for 60 minutes (heating and cooling profile as per the chapter)
Titrant0.01 M hydrochloric acid
IndicatorMethyl red
Result unitmL of 0.01 M HCl per 100 mL of extract
BEFORE YOU REPORT

System suitability & sequence

ParameterLimit
Autoclave cycleTemperature profile recorded and within the chapter's tolerances
BlankBlank titration on purified water performed and subtracted

Typical sequence

  1. 1Brimful capacity determination
  2. 2Filling and autoclaving of containers
  3. 3Blank titration
  4. 4Titration of extract aliquots
CALCULATION

Calculation with a worked example

Result (mL 0.01 M HCl per 100 mL) = (Vs − Vb) × 100 ÷ Va

Where

Vs
Volume of 0.01 M HCl used for the extract aliquot (mL)
Vb
Volume of 0.01 M HCl used for the blank (mL)
Va
Volume of extract titrated (mL)

Given

Va
50.0 mL
Vs
0.42 mL
Vb
0.02 mL

Working

  1. Net titre = 0.42 − 0.02 = 0.40 mL
  2. Per 100 mL = 0.40 × 100 ÷ 50.0 = 0.80 mL of 0.01 M HCl per 100 mL
  3. Compare 0.80 mL with the limit in the current chapter for this filling volume and glass type

0.80 mL of 0.01 M HCl per 100 mL of extract (illustrative). Judge against the limit table for the container size and glass type in the current chapter.

ACCEPTANCE CRITERIA

What result passes

  • The result does not exceed the limit given in the current USP <660> / Ph. Eur. 3.2.1 table for the container's filling volume and declared glass type (Type I and II share the tighter limits; Type III has wider limits). See the current chapter.
  • Where the glass type needs confirming, the glass grains test (bulk glass) and surface etching test distinguish Type I from Type II and III.
METHOD VALIDATION

Validation parameters (ICH Q2(R2))

ParameterTypical requirement
ApproachCompendial test; verify autoclave performance, titrant factor and water quality
AutoclaveQualified and able to follow the specified heating, holding and cooling profile
PrecisionReplicate titrations agree within the SOP limit
In LimsPulse · Sample Management

Run this method in LimsPulse: specifications and STPs under version control, results calculated and checked against limits, and a signed Certificate of Analysis.

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