RISE offers dissolution analyses for formulations such as tablets and capsules under development or for GMP quality control of finished product. We perform method development, method validation and tech transfer of existing methods, we focus on robust arrangements adapted to the product, the dosage form and regulatory requirements.

Dissolution analysis is used to show how quickly and to what extent a substance is released from, for example, a tablet under defined conditions.  

The testing is used in formulation development as well as process development, and as part of quality control for the finished product. 

Dissolution analyses are performed on both immediate release dosage forms and extended and delayed release dosage forms.

RISE can perform: 

• dissolution testing for tablets and capsules, as well as other formulations on request
• method development and optimisation adapted to product and area of use 
• method validation and tech transfer of existing methods
• support in formulation and process development
• routine analyses according to GMP   

Dissolution testing is performed primarily according to the pharmacopoeial method Ph. Eur. 2.9.3 and USP <711>. These are harmonised for dissolution testing of oral solid formulations.                         We perform analyses mainly on tablets and capsules, but other formulations are also possible.             

Instrument

Our automated dissolution instrument is qualified for GMP analysis and equipped with extraction probes, temperature monitoring in all vessels and the possibility of automated filtration of release samples. The automation contributes to high reproducibility and efficient sample handling.  

The analysis is done either with rotating paddles or baskets, which is most common for tablets and capsules. Samples are withdrawn at defined times. Quantification of released substance is mainly done with LC UV or LC CAD, depending on the product's properties.

Reporting is done by agreement and can include anything from a simple performance report to a full analytical method validation report or tech transfer report. We adapt the structure and documentation to the phase of the project, the customer's needs and applicable regulatory requirements.

RISE offers determination of organic solvent residues with Headspace GC in solid and liquid samples. The analysis can be performed to GMP quality level according to ICH Guidelines for drug substance and drug product, according to Ph Eur 2.4.24, or exploratory.

Residual solvent analysis aims to ensure the safety, quality and regulatory compliance of products and processes where organic solvents are used.  

The analysis is a tool in, for example, work to protect health and the environment, to maintain high product quality and to comply with laws and standards, especially in the areas of pharmaceuticals, food, chemistry and the environment.  

Areas of application 

• Safety. Organic solvents can cause negative effects on health and the environment. The analysis ensures that the levels are below permitted limits.
  • Monitoring: Analysis of solvent residues as part of the monitoring of solvent emissions and exposures to protect the environment and personnel                                                                                       
• Quality control. Residues of solvents in a product can affect the stability, taste, smell or function of the product. Analysis verifies that manufacturing produces a clean and consistent product.
  • Pharmaceuticals: Ensuring that the active substance and finished product do not contain harmful levels of residual solvents from the manufacturing process
  • Food and packaging: Control of solvents from printing inks and adhesives in the packaging that can migrate to the food                                                                                                              
• Regulatory compliance. Legislation and guidelines, such as ICH Q3C for pharmaceuticals or food law within EU, set maximum limits for residual solvents. Analysis is required to demonstrate compliance.                    
• Process optimisation. The analysis results can be used to improve process steps such as drying or purification in a manufacturing process, to reduce solvent residues and make the process more efficient.

Gas chromatography (GC) is the standard method for the analysis of solvent residues. The most widely used technique is Headspace GC (HS GC), where a dissolved sample is heated and volatile organic solvents are analyzed in the gas phase. The most common detection technique is Flame Ionisation Detection (FID).   

The method is quantitative, robust, highly reproducible and standard in quality control QC. Furthermore, the method is very sensitive, solvent concentrations at ppm and down to ppb levels can be analysed, and it is suitable for volatile and semi volatile organic solvents.  

RISE performs both GMP analyses according to ICH Guidelines (ICH Q3C), analyses according to Ph Eur 2.4.24 and exploratory analyses for research and development purposes.  

Results are reported in agreement with the customer, for example in the form of a written report, or a Certificate of Analysis CoA, or as a table with raw data.

RISE offers determination of water content by Karl Fischer titration (KF) in solids and liquids.
Analyses can be performed to GMP quality level according to Ph Eur for drug substance and drug product, or exploratory.

The presence of water in a product can, for example, affect the quality and shelf life of pharmaceuticals and food, the course of reactions in chemical processes, and the safety and function of oils, fuels and solvents.  

With Karl Fischer titration, the water content (moisture content) of solids or liquids is determined both qualitatively and quantitatively with very high accuracy. Content levels from trace amounts up to percentages of a water can be analyzed. 

RISE performs both GMP analyses according to the European Pharmacopoeia Ph Eur and exploratory studies for research and development purposes.   

Karl Fischer titration is a fast, selective, and precise method for water content determination. It is a standard method in the pharmaceutical industry, chemical industry, food analysis, petrochemistry and quality control laboratories. 

Two method variants can be performed:  

• Volumetric Karl Fischer titration (GMP according to Ph Eur 2.5.12), for samples containing water at 0.1 – 100%
• Coulometric Karl Fischer titration (GMP according to Ph Eur 2.5.32), for samples with very low water contents, down to ppm levels

Results are reported in agreement with the customer, for example in the form of a written report, as a Certificate of Analysis CoA, or as a table with raw data.

RISE offers analyses according to GMP or exploratory of Specific surface area using the Brunauer-Emmett-Teller (BET) method to gain information about a material's reactivity. Also measurements of Pore size and Pore size distribution. Analysis on solid samples such as powders, tablets, porous materials and catalysts.

The specific surface area of a solid provides information about the reactive properties of the material. The dissolution rate of a drug is often correlated to the specific surface area, and the same applies to performance of, for example, batteries and catalysts.                                                   By measuring Specific surface area, information is obtained regarding the quality and functionality of the material.  

The sample is prepared for analysis by degassing under vacuum at an elevated temperature or in a stream of inert gas, such as nitrogen.   

 During the analysis, inert gas molecules with a known area, such as nitrogen, are introduced to the sample. This is done in several rounds in a certain amount and to a certain pressure. The surface area of the sample is then determined by measuring exactly how many gas molecules are needed to adsorb directly onto the surface of the sample and first covering it in a so-called monolayer, and then in multilayers.  

The specific surface area is then calculated based on the mass of the sample.   

Using BET, RISE can analyse: 

• Specific surface, Pore size and Pore size distribution
• according to GMP quality level or exploratory
• on solids such as powders, tablets, porous materials, catalysts                                                                                                                                                                                                                                   

Results in report format as agreed with client.

RISE offers stability studies for quality evaluation of a product or substance during storage.
Samples are held at 25°C/60%RH, 40°C/75%RH, 5°C or -18°C in validated climate cabinets/fridge-freezers with continuous monitoring, temperature and humidity log.
Studies performed GMP according to ICH Guidelines on drug substance/product, or exploratory.

Stability studies are performed on chemical substances and on products such as pharmaceuticals, food, beverages and cosmetics to map the quality of the material over time. Factors that may affect quality include temperature, humidity and light. The result of the studies can be used to determine shelf-life, re-test date or recommended storage conditions.

Representative samples of the material, with a specified quality by reference to parameters such as appearance, content, chemical purity, pH, are placed in specific environments over a selected period of time. The quality of the material is monitored during the period by sampling at certain times, the samples are analysed according to the specified quality parameters and results are compared with the original values.

RISE conducts both regulatory GMP studies according to ICH guidelines (ICH Q1A), or exploratory studies for research and development purposes.   Both short-term studies (weeks) and long-term studies (several years) are possible.

RISE can offer the following environments for stability studies: 

• 25°C±2°C / 60%±5% RH, standard
• 40°C±2°C / 75%±5% RH, accelerated
• 5°C±3°C, fridge
• -20°C±5°C, freezer

Climate cabinets have controlled temperature and humidity, fridge/freezers controlled temperature. They are qualified according to GMP requirements and placed in a room only accessible to authorized personnel. Humidity and temperature are electronically logged and stored in cloud storage in a web-based system. In the event of temperature or humidity outside specified interval, the system alerts responsible personnel via e-mail or text message around the clock.

RISE can also perform several types of analyses according to GMP on sampled material, e.g. assay and purity (LC, GC, NMR), appearance, water content (KF), pH. Samples can also be sent to external laboratories.                                                                                                                                                                

We can also develop and validate stability-indicating analysis methods, including forced degradation where the substance/product is exposed to heat, light, acid, base and oxidizing agent to induce formation of eventual degradation products.

A study plan is agreed upon with the customer before the start of the study. Interim reports can be issued during the course of the study and a summary stability report after study completion.                                                                                                                                      

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