What temperature and humidity conditions should be noted during the storage of cellulose pharmaceutical excipients? ​

Cellulose pharmaceutical excipients are commonly used excipients in drug production, and temperature and humidity are the core control indicators during storage. At the same time, key requirements such as moisture resistance, light avoidance, and pollution prevention should also be taken into account. Once the temperature and humidity are out of control, it will directly affect the physical and chemical properties of the excipients, leading to substandard drug quality. Below are detailed key points for storage, all of which are practical and applicable for warehouse control and compliance acceptance.

Firstly, clarify the core principle: most cellulose pharmaceutical excipients belong to materials with strong moisture absorption and temperature sensitivity. The stored core temperature and humidity should be in line with their stable range. Different types of cellulose excipients have slightly different temperature and humidity requirements, but there is a unified compliance standard. First, clarify the general requirements, and then explain the special precautions for segmented categories.

1、 Universal temperature and humidity core standards (applicable to the vast majority of cellulose pharmaceutical excipients)

This is a fundamental requirement in pharmacopoeia and pharmaceutical production quality management standards, which is the bottom line for storage and must be strictly followed

Temperature control: The core range is 15 ℃~25 ℃, and short-term fluctuations are allowed (such as temporary transportation or warehouse regulation), but the fluctuation range cannot exceed 5 ℃. Two are prohibited: one is that the temperature is below 0 ℃, and low temperature will cause some cellulose excipients to crystallize and precipitate, and the toughness will decrease. For example, carboxymethyl cellulose sodium is prone to agglomeration at low temperatures, and subsequent feeding is difficult to disperse; Secondly, temperatures above 30 ℃ can accelerate the degradation of cellulose, damage its molecular structure, and cause a decrease in viscosity and poor flowability. For example, after being stored at high temperatures, the effectiveness of hydroxypropyl methylcellulose as a disintegrant or adhesive will significantly decrease, affecting the disintegration time and hardness of the tablets.

Humidity control: The core range is 45% RH~65% RH, which is a key control indicator because cellulose excipients naturally absorb moisture, and the impact of humidity control is more direct than temperature. If the humidity is below 45% RH, it will cause the auxiliary materials to become too dry, resulting in dust emissions. This not only leads to significant losses during feeding, but may also affect workshop dust control; Humidity above 65% RH is a major taboo, as it can cause a series of problems such as moisture absorption and clumping, decreased fluidity, excessive moisture content, and even the growth of microorganisms (pharmaceutical excipients have strict requirements for microbial limits). For example, microcrystalline cellulose may clump after absorbing moisture, making it difficult to mix evenly and resulting in uneven drug content; Sodium carboxymethyl cellulose will become sticky after absorbing moisture and lose its practical value directly.

2、 Special requirements for temperature and humidity of different categories of cellulose pharmaceutical excipients (targeted control to avoid one size fits all)

Common cellulose medicinal excipients are divided into several categories, with slight emphasis on temperature and humidity requirements due to structural differences. When storing, targeted adjustments should be made to meet the specifications and usage needs

Microcrystalline cellulose (MCC): a commonly used filler and disintegrant. The temperature and humidity should follow the general standards. It is recommended to control the humidity between 50% RH and 60% RH for stability. If the humidity exceeds 65% RH, it is prone to moisture absorption and clumping. Even if crushed, it is difficult to restore the original fluidity and will affect the disintegration performance; The temperature should be kept as stable as possible between 18 ℃ and 22 ℃ to avoid frequent temperature fluctuations, which can cause condensation on the surface of the auxiliary materials and indirectly lead to moisture absorption.

Carboxymethyl cellulose sodium (CMC Na): commonly used adhesive and suspension aid, with strong hygroscopicity, belonging to the "high sensitivity type". The humidity must be strictly controlled between 45% RH and 60% RH, and cannot exceed 60% RH. Once it exceeds the standard, it will quickly absorb moisture, become sticky, and even swell; The temperature should be controlled between 15 ℃ and 23 ℃. High temperatures can accelerate the hydrolysis of ether bonds, leading to a decrease in viscosity. For example, when used as an oral suspension aid, insufficient viscosity can result in layered precipitation.

Hydroxypropyl methylcellulose (HPMC): a commonly used film coating material, adhesive, and sustained-release skeleton material that is sensitive to temperature and humidity. The temperature should be controlled first between 15 ℃ and 20 ℃. High temperatures can damage its sustained-release structure, affect the permeability and stability of the coating film, and result in unsatisfactory release of sustained-release tablets; Humidity control between 45% RH and 60% RH can cause uneven film formation, flower spots, and cracking during coating after moisture absorption.

Hydroxypropyl cellulose (HPC): commonly used adhesive and disintegrant, with moderate moisture absorption. The temperature and humidity can follow general standards, but the temperature should not exceed 25 ℃. High temperatures can cause a decrease in its solubility, making it difficult to dissolve evenly during feeding; The humidity should be controlled between 50% RH and 65% RH, without excessive strictness, but long-term exposure to high humidity environments should be avoided.

Ethyl cellulose (EC): a commonly used slow-release coating material and skeleton material, belonging to hydrophobic cellulose excipients, with weak moisture absorption and relatively relaxed temperature and humidity requirements. The temperature can be relaxed to 10 ℃~30 ℃, and the humidity should be controlled between 40% RH~70% RH. However, two points should be noted: first, avoid high temperature exposure to sunlight, which can cause its color to turn yellow and affect the appearance of the drug coating; The second is to avoid sudden fluctuations in humidity and prevent surface condensation.

Methylcellulose (MC): commonly used adhesive and suspension aid, with strong hygroscopicity, temperature control of 15 ℃~25 ℃, easy gelling at low temperature and easy degradation at high temperature; The humidity is strictly controlled between 45% RH and 60% RH, and the viscosity is unstable after moisture absorption, which affects the effectiveness of use.

3、 Key supporting precautions during storage, apart from temperature and humidity control, are indispensable

Temperature and humidity are the core, but controlling temperature and humidity alone is not enough. It is also necessary to do a good job in supporting control to ensure the stable storage of cellulose pharmaceutical excipients and meet pharmaceutical standards

Light shielded storage: All cellulose pharmaceutical excipients should be kept away from light, especially those containing hydroxyl and ether bonds (such as HPMC, CMC Na). Ultraviolet radiation can accelerate molecular chain breakage, leading to degradation and deterioration. When storing, they should be stored in a cool and light shielded warehouse. The packaging of excipients should be made of materials with good light shielding properties (such as aluminum foil bags and light shielding composite bags), and it is forbidden to use transparent plastic bags for direct packaging. The warehouse windows should be covered with light shielding film to avoid direct sunlight.

Sealed packaging: This is a prerequisite for temperature and humidity control. Before storage, it is necessary to check whether the packaging is sealed. Medicinal cellulose excipients are usually packaged in "inner polyethylene bag+outer kraft paper bag" or "aluminum foil composite bag". Poor sealing can directly cause moisture absorption and pollution. Unused excipients after unpacking should be promptly sealed and placed in a sealed container to avoid exposure to air. It is recommended to use them as soon as possible after unpacking, generally not exceeding 7 days.

Reasonable stacking: When stacking, it is necessary to be "off the ground and off the wall", with a height of not less than 10cm from the ground and not less than 30cm from the wall, to avoid the influence of moisture on the ground and water seepage on the wall on the auxiliary materials. The stacking height should not be too high, generally not exceeding 5 layers, to prevent the bottom auxiliary materials from being compressed and clumped. At the same time, a passage should be left for ventilation and temperature and humidity monitoring; Cellulose excipients of different categories and batches should be stacked separately and labeled to avoid mixing and cross contamination.

Real time monitoring of temperature and humidity: The warehouse must be equipped with accurate temperature and humidity recorders, calibrated according to regulations (at least once a year), and monitoring points should be arranged reasonably, such as placing them at the corners, middle, and different heights of the warehouse to ensure full monitoring coverage. Temperature and humidity should be recorded at least twice a day (once in the morning and once in the afternoon). Once the standard range is exceeded, timely control measures should be taken, such as turning off the dehumidifier when the humidity is high, turning on the air conditioning when the temperature is high, and doing insulation when the temperature is low.

Anti pollution and odor prevention: Cellulose excipients have strong adsorption properties, not only absorbing moisture but also adsorbing odors. Storage warehouses should be kept away from materials with odors and corrosiveness (such as acids, bases, and organic solvents) to avoid odor adsorption affecting the purity of excipients; At the same time, dust control measures should be taken, and the warehouse floor should be flat and clean, regularly cleaned to avoid dust pollution of auxiliary materials.

Moisture proof and Waterproof: The warehouse should be well waterproofed and leak proof to avoid water leakage and moisture regain on the ground during rainy days. Water blocking strips can be installed at the entrance of the warehouse, and moisture-proof filters should be installed at the ventilation openings. During the rainy season, the frequency of dehumidification should be increased to ensure that the humidity is stable within the standard range.

Compliant storage period: Store according to the expiration date of the auxiliary materials. It is strictly prohibited to use expired auxiliary materials. During the storage process, regular inspections should be carried out to observe the appearance of the auxiliary materials. If there are lumps, discoloration, stickiness, odor, etc., they should be immediately stopped and sent for inspection to confirm whether they have deteriorated.

4、 Common storage issues and emergency response (practical avoidance of pitfalls, quick resolution of anomalies)

Slight moisture absorption (appearance slightly damp, no clumping): Immediately transfer to a dry warehouse, unpack and spread open air to dry (strictly prohibited from exposure to sunlight or high temperature drying). After drying, check the moisture content and physical and chemical indicators. Only after passing the inspection can it be used, otherwise it will be scrapped.

Severe moisture absorption (clumping, sticking): scrapped directly and cannot be reused to avoid affecting the quality of the drug.

Temperature exceeding the standard (short-term above 30 ℃ or below 0 ℃): Immediately adjust the temperature and humidity of the warehouse. After the standard is restored, randomly check the viscosity, fluidity, moisture content and other indicators of the auxiliary materials. If they are qualified, they can continue to be used, and if they are unqualified, they will be scrapped.

Packaging damage: Immediately replace the sealed packaging. If it has been exposed to air, follow the moisture absorption process for inspection. If it is qualified for use, it will be scrapped if it is unqualified.

Finally, the core points are summarized as follows: storage of cellulose pharmaceutical excipients, dual control of temperature and humidity (generally 15-25 ℃, 45-65% RH, with targeted adjustments for different categories), basic packaging and sealing, light and moisture avoidance, supporting ground and wall separation, real-time monitoring, and regular inspections. All of these points can be achieved to ensure stable storage of excipients, meet pharmaceutical compliance requirements, and avoid deterioration of excipients and drug quality risks caused by improper storage.