Drug stability (e.g., oral suspensions, insulin, reconstitutables, injectables, vaccinations)
What is Drug stability?
Drug stability refers to the ability of a pharmaceutical product to maintain its chemical, physical, microbiological, and therapeutic properties within specified limits throughout its shelf life. Proper stability ensures safety, efficacy, and quality of medications.What is Shelf Life of a Drug?
The shelf life of a drug is the time period during which a medication remains safe, effective, and retains its intended quality when stored under recommended conditions. After this period, the drug may lose potency, degrade into harmful byproducts, or become unsafe for use.Which factors affect Drug Stability?
Chemical Degradation
- Hydrolysis (e.g., aspirin breaking down into salicylic acid)
- Oxidation (e.g., vitamin C degradation)
- Photolysis (light-induced breakdown, e.g., nitroprusside)
Physical Instability
- Changes in color, odor, hardness (tablets), or phase separation (creams).
- Example: Crystallization of insulin if improperly stored.
Microbiological Instability
- Growth of bacteria/fungi in liquid formulations (e.g., syrups, eye drops).
Environmental Factors
- Temperature (e.g., refrigeration for biologics like vaccines).
- Humidity (moisture can degrade tablets).
- Light (e.g., amber bottles for light-sensitive drugs).
- Oxygen exposure (antioxidants used in formulations).
Oral Suspensions Stability Issues
Oral suspensions are liquid formulations containing insoluble drug particles dispersed in a liquid medium. Their stability depends on physical, chemical, and microbiological factors that can affect their potency, efficacy, and safety.
Physical Stability (Sedimentation & Resuspension)
Issue: Particles settle over time, leading to inconsistent dosing.
Examples:
- Amoxicillin Suspension – Requires shaking before each use to ensure uniform dosing.
- Erythromycin Ethylsuccinate Suspension – Can form caking, making resuspension difficult.
Prevention:
- Use suspending agents (e.g., xanthan gum, carboxymethylcellulose).
- Instruct patients to shake well before use.
Chemical Stability
(Degradation & Hydrolysis)
Issue: Drug molecules may degrade due to hydrolysis, oxidation, or pH changes.
Examples:
- Amoxicillin-Clavulanate (Augmentin Suspension) – Clavulanic acid degrades quickly after reconstitution.
- Omeprazole Suspension – Acid-sensitive and unstable in liquid form.
Prevention:
- Store in refrigeration to slow degradation.
- Use buffering agents to maintain stability.
Microbiological Stability (Contamination & Preservation)
Issue: Liquid formulations are prone to bacterial & fungal contamination.
Examples:
- Nystatin Oral Suspension – Can support microbial growth if improperly stored.
- Cefdinir Suspension – Requires refrigeration or has a limited shelf life at room temperature.
Prevention:
- Use preservatives (e.g., parabens, sodium benzoate).
- Follow expiration guidelines after reconstitution.
Storage Guidelines for Oral Suspensions
Before Reconstitution (Dry Powder Form)
- Store at room temperature (15-25°C).
- Keep in airtight packaging to prevent moisture absorption.
- After Reconstitution (Liquid Form)
- Refrigeration required (e.g., Amoxicillin, Augmentin).
- Room temperature storage allowed (e.g., Azithromycin).
- Discard after 7-14 days (varies by product).
Patient Counseling Points for Oral Suspensions
✅ Shake well before each use to ensure proper dosing.
✅ Follow storage instructions (room temp vs. refrigeration).
✅ Discard after expiration to avoid degraded or ineffective medication.
✅ Measure accurately using a dosing syringe or spoon.
Insulin Stability Issues
Insulin is a temperature-sensitive peptide hormone that requires proper storage and handling to maintain its potency. Instability can lead to loss of effectiveness, or degradation, which can impact blood glucose control.
Temperature Sensitivity
Issue: Insulin loses potency when exposed to extreme heat or freezing temperatures. Examples:- Humulin, Novolog, Lantus – Lose effectiveness if stored above 30°C (86°F).
- Insulin Glargine (Basaglar, Toujeo) – Becomes unstable if frozen.
- Store unopened vials in the refrigerator (2-8°C / 36-46°F).
- Do not freeze insulin—discard if frozen.
- Keep in-use vials or pens at room temperature and use within 28-42 days, depending on the type.
Physical Instability (Aggregation & Denaturation)
Issue: Insulin is a protein that can denature or aggregate due to shaking or improper storage. Examples:- NPH & Regular Insulin (Humulin, Novolin) – Precipitates if shaken too vigorously.
- Insulin Detemir (Levemir) – Can form clumps or fibrils when stored improperly.
- Do not shake insulin vials or pens—roll them gently in your hands.
- Inspect for clumping, precipitation, or discoloration before use.
Light Sensitivity
Issue: Direct exposure to light can degrade insulin molecules. Examples:- Rapid-acting insulins (Lispro, Aspart, Glulisine) degrade faster under UV light.
- Store insulin in its original packaging until use.
- Avoid prolonged exposure to sunlight or artificial light.
Adsorption to IV Bags or Syringes
Issue: Insulin can bind to plastic surfaces, reducing the delivered dose. Examples:- Regular Insulin IV (Humulin R, Novolin R) – Adsorbs to PVC tubing in IV administration.
- Use non-PVC containers or special insulin-compatible tubing.
- Prime the IV tubing with insulin solution before administration.
Patient Counseling Points
✅ Store insulin properly – Refrigerate unopened vials/pens, keep in-use insulin at room temperature.
✅ Do not freeze insulin – Frozen insulin is no longer effective.
✅ Inspect before use – Do not use if insulin appears clumpy, cloudy (unless NPH), or discolored.
✅ Avoid extreme temperatures – Do not leave insulin in hot cars or direct sunlight.
✅ Gently roll cloudy insulin (e.g., NPH) instead of shaking it.
✅ Use insulin within recommended expiration once opened.
Injectables Stability Issues
Injectable medications (e.g., IV, IM, subcutaneous drugs) are sterile formulations that are directly administered into the body. Their stability is crucial because degradation can lead to loss of potency, safety issues, or formation of toxic by-products. Proper storage, handling, and administration are vital to maintain their therapeutic effect.
Oxidation
Issue: Exposure to oxygen can cause chemical degradation of active ingredients, especially in liquid formulations. Examples:- Epinephrine (Adrenaline) – Oxidizes to adrenochrome, causing discoloration and loss of potency.
- Vitamin K – Degrades when exposed to oxygen and light.
- Store in airtight containers or vials.
- Use antioxidants (e.g., sodium metabisulfite).
- Protect from light exposure using amber-colored vials.
Precipitation
Issue: Injectables can form precipitates when stored at improper temperatures or mixed with other medications. Examples:- Diazepam (Valium) – Precipitates at low temperatures or when diluted improperly.
- Calcium-containing solutions (e.g., calcium gluconate) – Can form precipitates when mixed with certain medications (e.g., phosphate salts).
- Follow recommended storage temperatures (usually room temperature or refrigerated).
- Avoid mixing incompatible drugs in IV lines.
- Inspect for precipitates before administration.
Adsorption to Containers or Tubing
Issue: Some drugs adsorb to plastic surfaces (e.g., PVC), reducing the amount of drug administered. Examples:- Nitroglycerin IV – Adsorbs to PVC tubing, reducing the dose delivered to the patient.
- Insulin – Adsorbs to IV bags or syringes, affecting delivery of dose.
- Use non-PVC containers or special tubing (e.g., glass, non-PVC plastic).
- Prime tubing before administration to minimize loss.
pH Sensitivity
Issue: Many injectables are sensitive to changes in pH, leading to precipitation or degradation. Examples:- Insulin – Precipitates or loses potency if the pH is outside the recommended range.
- Phenytoin (Dilantin) – Highly pH-sensitive, causing precipitation in solutions with lower pH.
- Maintain proper pH ranges as specified in product labeling.
- Use buffered solutions to stabilize pH.
Microbial Contamination
Issue: Injectables are vulnerable to bacterial or fungal contamination if not stored or handled properly. Examples:- Multidose vials (e.g., Diazepam, Heparin) – Risk of contamination if sterility is compromised.
- IV Fluids (e.g., Dextrose) – Prone to microbial growth if improperly stored.
- Use aseptic techniques during preparation and administration.
- Use preservatives in multi-dose vials.
- Store in sterile, sealed containers.
Important Considerations for Injectable Storage
- Refrigeration (2-8°C): Many injectable medications, especially antibiotics and biologics, require refrigeration to maintain their potency and prevent degradation.
- Room Temperature (15-25°C): Some injectables, such as certain anesthetics or pain medications, are stable at room temperature but should be protected from light and moisture.
- Avoid Freezing: Freezing can cause protein-based injectables (e.g., insulin, vaccines) to lose potency or become denatured. Always discard if frozen.
- Light Sensitivity: Protect sensitive injectables from light by storing in amber vials or opaque containers.
- Shelf-Life After Opening: Follow the manufacturer’s recommendations regarding the shelf-life after the vial or container has been opened. Multiple-dose vials often have a shorter shelf-life once exposed to air or handling.
- Prime IV Lines: When using IV lines for certain medications, especially those prone to adsorption, it’s important to prime the line with the drug to minimize loss.
Vaccination Stability Issues
Vaccines are biological preparations designed to provide immunity against diseases by stimulating the immune system. Their stability is vital because degradation due to temperature fluctuations, light exposure, or contamination can render the vaccine ineffective or unsafe. Ensuring proper storage and handling is crucial to maintain their potency and safety.
Temperature Sensitivity (Cold Chain Requirements)
Issue: Vaccines are highly sensitive to temperature variations, and extreme heat or freezing can degrade the active ingredients, making them ineffective. Examples:- mRNA Vaccines (Pfizer, Moderna COVID-19) – Require storage at -70°C to -80°C to maintain stability.
- Measles, Mumps, Rubella (MMR) – Requires refrigeration at 2-8°C; freezing destroys potency.
- Diphtheria, Tetanus, and Pertussis (DTP) – Must be stored between 2-8°C, as freezing can damage the vaccine.
- Strict cold-chain storage from manufacturing to administration.
- Use data loggers to monitor temperatures during transport and storage.
- Store vaccines in refrigerators or freezers designed for temperature-controlled environments.
Light Sensitivity (Photodegradation)
Issue: Some vaccines degrade when exposed to light, particularly UV light, which can break down the active components. Examples:- Bacillus Calmette–Guérin (BCG) – Sensitive to light; must be stored in dark conditions.
- Rotavirus vaccines – Require protection from light to preserve effectiveness.
- Store vaccines in opaque containers or protective packaging.
- Avoid exposure to light, especially direct sunlight or artificial UV light.
Chemical Instability (Degradation of Components)
Issue: Some vaccine components may degrade due to chemical reactions such as hydrolysis, oxidation, or pH changes. Examples:- Influenza vaccines (Flu shots) – Can degrade if exposed to temperature fluctuations or pH changes during reconstitution.
- Pneumococcal vaccines – Degradation may occur due to oxidation of certain components.
- Store vaccines according to the manufacturer’s guidelines (temperature, pH range, etc.).
- Avoid shaking or agitating vaccines as it can affect their stability.
Microbial Contamination (Aseptic Handling)
Issue: Contamination during handling or preparation can introduce microbes, affecting vaccine sterility and safety. Examples:- Multi-dose vials – Prone to microbial contamination if not handled aseptically.
- Live vaccines (e.g., Oral Polio Vaccine) – Risk of bacterial contamination if improperly handled.
- Use aseptic techniques during reconstitution and administration.
- Single-use vials should be discarded after one use to prevent contamination.
Key Points for Vaccine Stability
- Cold Chain Storage: Ensure vaccines are stored at the proper temperature (e.g., 2-8°C for most vaccines) and never freeze vaccines unless specified.
- Use Data Loggers: Monitor temperature continuously during transport and storage.
- Light Protection: Store vaccines in dark places or opaque packaging to protect them from light degradation.
- Strict Handling Procedures: Use aseptic techniques to prevent contamination during reconstitution or injection.
- Shelf Life Compliance: Ensure that vaccines are used within the recommended time after reconstitution, as the potency can decline over time.
- Labeling and Documentation: Properly label and track vaccine storage conditions to ensure that vaccines haven’t been exposed to unsuitable conditions.
Handling Vaccines for Pharmacy
✅ Store vaccines in their original packaging and keep them refrigerated or frozen according to the manufacturer’s instructions.✅ Inspect for any precipitation or discoloration before use.
✅ Avoid freezing vaccines unless specified (e.g., mRNA COVID-19 vaccines).
✅ Record and monitor storage conditions regularly, especially for multi-dose vials.
✅ Do not use expired vaccines or those that have been stored improperly.
Reconstitutables vs Suspensions: Key Differences
Reconstitutables are medications that are initially provided in a lyophilized (freeze-dried) form or as a powder and must be reconstituted (mixed) with a solvent (e.g., water, saline) before administration. Stability of these medications is critical because improper reconstitution or storage can lead to loss of potency, precipitation, or bacterial contamination.
Reconstitutables:
These are medications that are provided in a dry powder or lyophilized form and need to be mixed (reconstituted) with a solvent (e.g., water, saline) before they can be administered. Common Examples:- Penicillin G (IV)
- Ceftriaxone (IV)
- Amphotericin B (IV)
Oral Suspensions:
These are liquid preparations in which the drug particles are suspended in a liquid medium but do not completely dissolve, leading to a heterogeneous mixture that needs to be shaken before use. Common Examples:- Amoxicillin Suspension
- Ibuprofen Suspension
- Hydrocodone/Acetaminophen Suspension
Reconstitutables Stability Issues
Degradation After Reconstitution
Issue: Once reconstituted, some medications may have a limited shelf life, during which they must be used within a specific timeframe to maintain effectiveness. Examples:- Penicillin G (potassium) – Once reconstituted, it must be used within 24 hours (stored in the refrigerator).
- Ceftriaxone (Rocephin) – Stable for 24 hours after reconstitution when refrigerated.
- Ampicillin – After reconstitution, stability is limited to 8 hours at room temperature and 24 hours when refrigerated.
- Use promptly after reconstitution according to specific instructions.
- Refrigerate after reconstitution when indicated by the manufacturer.
- Discard any unused portion after the expiration time.
Microbial Contamination
Issue: Reconstituted drugs can be prone to microbial growth if not handled under sterile conditions or stored properly. Examples:- Cephalosporins (e.g., Cefazolin, Ceftriaxone) – Risk of microbial contamination if reconstituted outside of a sterile environment.
- Vaccines and biologics – After reconstitution, they are susceptible to bacterial contamination.
- Follow aseptic techniques during reconstitution.
- Use sterile water or saline for reconstitution as per product guidelines.
- Store reconstituted products in refrigerators as recommended and avoid contamination.
Precipitation or Physical Instability
Issue: Some medications may precipitate when reconstituted, particularly if not prepared or stored correctly. Examples:- Diazepam (Valium) – Precipitates if diluted with an incompatible solvent or stored improperly.
- Amphotericin B – Precipitates at lower temperatures after reconstitution.
- Follow reconstitution instructions carefully, including the choice of solvent.
- Store reconstituted drugs at recommended temperatures (refrigeration or room temperature).
- Ensure that the solvent is compatible with the medication.
pH Sensitivity
Issue: Some medications are sensitive to pH changes, and incorrect reconstitution can lead to instability or degradation of the drug. Examples:- Phenytoin (Dilantin) – Highly pH-sensitive; improper dilution or reconstitution leads to precipitation.
- Gentamicin (IV) – Stability is affected by pH levels when reconstituted improperly.
- Use the specified solvent and pH buffer if indicated.
- Follow pH range specifications for reconstituted drugs.
Key Considerations for Stability of Reconstitutables
- Correct Solvent Use: Always use the recommended solvent for reconstitution. Some medications require water for injection, while others may need normal saline or dextrose solution.
- Aseptic Techniques: Reconstituted drugs must be prepared in sterile conditions to avoid contamination, especially for multi-dose vials.
- Temperature Control: Store reconstituted drugs at the correct temperature (typically 2-8°C for refrigeration). Room temperature may be acceptable for some drugs but should be carefully followed as per product instructions.
- Proper Labeling: After reconstitution, label the vial with the date and time of reconstitution to monitor the expiration of the drug’s potency.
- Avoid Freezing: Some reconstituted medications are sensitive to freezing and should be stored in a refrigerator at 2-8°C.
Drug Stability in Various Dosage Forms
| Dosage Form | Key Stability Issues | Storage Guidelines |
| Aerosols/Inhalers | Propellant loss, moisture contamination | Keep at room temperature, avoid extreme heat or cold |
| Capsules | Moisture sensitivity, heat degradation, shell brittleness | Store in airtight containers in a dry, cool place |
| Ear Drops | Microbial growth, temperature sensitivity | Keep in cool, dry place, avoid contamination |
| Eye Drops | Contamination risk, oxidation | Store in sterile conditions, refrigerate if required |
| Injectable Solutions | Oxidation, precipitation, light sensitivity, contamination | Store per manufacturer instructions (room temp/refrigeration) |
| Insulin | Heat sensitivity, degradation if frozen | Refrigerate before use, keep at room temp after opening |
| Nasal Sprays | Microbial contamination, evaporation | Keep bottle tightly sealed, store as directed |
| Oral Solutions | Microbial growth, oxidation, evaporation | Store in tightly closed bottles, avoid heat exposure |
| Oral Suspensions | Sedimentation, microbial contamination, degradation over time | Refrigerate if required, shake well before use |
| Powders for Reconstitution | Moisture sensitivity, degradation over time | Store in dry conditions, use promptly after mixing |
| Reconstitutable Injectables | Short shelf-life after mixing, risk of contamination | Use immediately or as directed, store in refrigerator if needed |
| Sublingual/Buccal Tablets | Moisture sensitivity, rapid degradation in humidity | Keep in airtight containers, avoid moisture |
| Suppositories | Melting, heat sensitivity | Store in cool place (refrigeration if needed) |
| Tablets | Moisture absorption, light sensitivity, temperature effects | Store in a cool, dry place, away from light and humidity |
| Topical Creams | Microbial contamination, light and air exposure, separation | Keep in original tube/jar, protect from heat and light |
| Topical Gels | Evaporation, pH changes, microbial contamination | Seal tightly after use, store in cool, dry place |
| Topical Ointments | Moisture absorption, oxidation, phase separation | Store in tightly sealed containers in a cool, dry place |
| Transdermal Patches | Adhesive breakdown, heat sensitivity | Store at room temperature, avoid excessive heat |
| Vaccines | Temperature sensitivity (cold chain required), light exposure | Refrigerate (2°C – 8°C), do not freeze |
Drug Stability for GLP-1 Drugs (GLP-1 Receptor Agonists)
GLP-1 receptor agonists are a class of medications used primarily for the management of type 2 diabetes and weight management. These drugs mimic the effects of the naturally occurring glucagon-like peptide-1 (GLP-1). These drugs helps regulate blood sugar levels and appetite.
Stability Concerns for GLP-1 Drugs
- Protein Degradation: GLP-1 receptor agonists are typically peptide-based medications (proteins or analogs) and are therefore susceptible to degradation through proteolysis (breakdown by enzymes), which can affect their potency.
- Temperature Sensitivity: GLP-1 drugs are highly sensitive to temperature fluctuations. They require refrigeration for storage and can lose potency if exposed to high temperatures or freeze.
- Light Sensitivity: Some GLP-1 drugs are sensitive to light, which can lead to degradation and loss of efficacy over time.
- Shelf Life: Due to their protein-based nature, GLP-1 drugs typically have a limited shelf life. They must be used within a specific time frame to maintain their therapeutic effects.
- Vial/Cartridge Integrity: Pre-filled pens or vials of GLP-1 receptor agonists may lose their stability if damaged, especially due to mechanical stress, cracking, or leaks.
GLP-1 Drugs Stability Comparison
| Drug Name | Storage Before Opening | Storage After Opening | Stability Considerations |
| Exenatide (Byetta) | Refrigerate (2°C to 8°C) | Room temperature for 30 days | Degradation if exposed to heat or freezing |
| Exenatide (Bydureon) | Refrigerate (2°C to 8°C) | Use immediately after mixing | Precipitation after reconstitution, light-sensitive |
| Liraglutide (Victoza) | Refrigerate (2°C to 8°C) | Room temperature (below 30°C) | Degradation if exposed to high temps or freezing |
| Semaglutide (Ozempic) | Refrigerate (2°C to 8°C) | Room temperature for 56 days | Loss of efficacy if exposed to temperature extremes |
| Dulaglutide (Trulicity) | Refrigerate (2°C to 8°C) | Room temperature for 14 days | Degradation if exposed to light or high temps |
| Albiglutide (Tanzeum) | Refrigerate (2°C to 8°C) | Use immediately after reconstitution | Degradation if not used after mixing, light-sensitive |
