Reduced stability study design for herbal product „dry cannabis floss“

Stability of the final product, independently whether it is an active substance or a drug of herbal, mineral or other origin, according to the guide of the International Conference for Harmonization (ICH): "Stability testing of new drug substances and products Q1A(R2)" is defined as the ability of the final product to keep the quality (physical-chemical and microbiological) prescribed in the specification for quality within the expiry date if it is stored in the proposed packaging. Stability testing enables the establishment of recommended storage conditions, retesting period, or expiry date for the product. When it comes to determining the stability of a herbal product, the procedure is more complex, taking into account the inhomogeneity of herbal preparations, which depends on many factors. This is also the case with cannabis-based preparations, especially dried cannabis flowers, which can be very heterogeneous depending on the variety. Therefore, it is necessary to test the stability of such products with a precisely defined protocol, a properly selected series of flowers, properly selected parameters to be monitored and the justification of the choice of parameters. In such cases, the guide provides accurate guidance for developing a stability protocol using a reduced design that simultaneously provides more information about the quality of the product packaged in several different packages, while significantly reducing the number of analyzes performed. In this way, the manufacturer using this design has an advantage in terms of reduced financial burden, reduced time constraints for obtaining data and rapid scientific expertise for decision making. In this direction, the aim of our research was to develop a protocol for monitoring the stability of dried cannabis flowers in different sizes from the same package using a reduced design, according to the guidelines of the International Council for Harmonization for the preparation of this type of stability study. During creating the protocol, the following topics were taken into account: specifications and certificates on the quality of the materials used for the final packaging of the herbal product, technological files for each produced batch of flowers that are tested for stability, as well as procedures and instructions for the process of growing and processing the flower . The stability study included batches of the final plant product - dried cannabis flower, with the same potency, or uniform content of the active component with proven therapeutic activity (tetrahydrocannabinol), so that the results would be comparable. The final product, dried cannabis flower, was packaged in multi-layer aluminum packaging in three different sizes. A stability protocol was developed in a way to includ different sampling frequencies from different packaging size, using bracketing and matrix principles. When carrying out the reduced design of the stability study, it was considered that the deviation of any parameter at any point of the test would mean a further extension of the test to obtain more relevant data to support the proposed packaging in the appropriate shelf lif

Forced degradation of timolol maleate on high temperature for verification of HPLC method for related substances in Timolol eye drop 0.5%

Timolol is a potent β-adrenergic blocker, useful in treatment of ocular hypertension or open-angle glaucoma. Many chromatographic analysis methods have been applied for the determination of pharmaceutical compounds containing heterocyclic rings (as timolol maleate), but the most commonly applied chromatographic technique is HPLC. Understanding the stability characteristics for both the active pharmaceutical ingredient (API) and for the drug product (DP) is crucial for the development of a safe and effective pharmaceutical agent. For this purpose, samples from API and DP during product development are disposed under strictly controlled storage conditions to assess stability testing. Forced degradation studies are being conducted to identify the degradation products that are likely to occur during long term storage as the worst- case scenario

Forced degradation of timolol maleate on high temperature for verification of HPLC method for related substances in Timolol eye drop 0.5%

Timolol is a potent β-adrenergic blocker, useful in treatment of ocular hypertension or open-angle glaucoma. Many chromatographic analysis methods have been applied for the determination of pharmaceutical compounds containing heterocyclic rings (as timolol maleate), but the most commonly applied chromatographic technique is HPLC. Understanding the stability characteristics for both the active pharmaceutical ingredient (API) and for the drug product (DP) is crucial for the development of a safe and effective pharmaceutical agent. For this purpose, samples from API and DP during product development are disposed under strictly controlled storage conditions to assess stability testing. Forced degradation studies are being conducted to identify the degradation products that are likely to occur during long term storage as the worst- case scenario

Pharmacoepidemiology and antimicrobial resistance data for bacterial infections in hospitalized children

Antimicrobial resistance is a global problem that needs an urgent action. The irrational use of antibiotics is widespread and leads to potential usefulness of medicines and negative therapeutic outcome.In April 2016, WHO stated that the problem of antibiotic resistance is a major clinical problem resulting in treatment failures even in a case ofeasy to treat diseases. Resistance to first line medicines results in huge spending on new generation of antibiotics. In some instances resistance to second- and third-line agents is seriously compromising treatment outcome.Seriousness of the situation requires extensive research and constantly monitoring of the spread of bacteria resistance.Another problem regarding bacteria resistance is the lack of new antibiotics reported by the US Center for Control and Prevention of Disease.A systematic literature search of databasesgave us enough information about the use of antibiotics, most often isolated bacteria and resistance to different classes of antibiotics. According to the official data, bacterial resistance is lowest in the countries where guidelines for prescribing and use of antibiotics are consistently implemented, such as Scandinavian countries, The Netherlands, Germany and Great Britain. It is necessary to create a complete database of bacterial resistance and information on whether patients receive medicines appropriate to their clinical condition in our country

Risk analysis for the presence of pesticides in dry cannabis floss cultivated under indoor conditions

Prospective risk analysis methods have significant potential for risk reduction and should be an integral part of any patient safety improvement strategy. Risk management principles are effectively utilized in many areas. In the pharmaceutical industry risk is defined as the combination of the probability of occurrence and the severity of the damage it can cost. To meet regulatory and quality control standards, cannabis products should be tested for all pesticides, especially high-risk pesticides to health. Determination of pesticides in cannabis facilities is increasingly important as medicinal uses of cannabis products expand rapidly. Therefore, risk analysis as a systematic process for detection of probability occurrence of harm can improve the decision making if a quality problem arises

Risk analysis for the presence of pesticides in dry cannabis floss cultivated under indoor conditions

Prospective risk analysis methods have significant potential for risk reduction and should be an integral part of any patient safety improvement strategy. Risk management principles are effectively utilized in many areas. In the pharmaceutical industry risk is defined as the combination of the probability of occurrence and the severity of the damage it can cost. To meet regulatory and quality control standards, cannabis products should be tested for all pesticides, especially high-risk pesticides to health. Determination of pesticides in cannabis facilities is increasingly important as medicinal uses of cannabis products expand rapidly.  Therefore, risk analysis as a systematic process for detection of probability occurrence of harm can improve the decision making if a quality problem arises

The Difference Between Verification and Validation of Analytical Methods in The Pharmaceutical Industry

To submit a dossier for marketing authorization to the Regulatory affairs, a product owner must provide Common Technical Documentation (CTD) containing a pharmaceutical product characteristics, manufacturing, quality control, safety (nonclinical), and efficacy (clinical) testing results before gaining approval for market access. Although quality improvement measures in the quality control laboratory have been enormous in recent years, especially due to improved handling of the validation and verification of the method performance, they often still differ widely from laboratory to laboratory. Much of what has been published on this topic is difficult to apply in routine laboratories due to complex statistics. The result is that method validation is often implemented incorrectly, which leads to false conclusions about the performance of the method, potentially compromising patient safety. The purpose of qualification, validation and verification is to generate reliable data for the products tested, resulting in the delivery of quality drug products to the patients. Therefore, the aim of this research is to emphasize the differences between verification and validation of analytical methods in the pharmaceutical industry

The difference between verification and validation of analytical methods in the pharmaceutical industry

To submit a dossier for marketing authorization to the Regulatory affairs, a product owner must provide Common Technical Documentation (CTD) containing a pharmaceutical product characteristics, manufacturing, quality control, safety (nonclinical), and efficacy (clinical) testing results before gaining approval for market access. Although quality improvement measures in the quality control laboratory have been enormous in recent years, especially due to improved handling of the validation and verification of the method performance, they often still differ widely from laboratory to laboratory. Much of what has been published on this topic is difficult to apply in routine laboratories due to complex statistics. The result is that method validation is often implemented incorrectly, which leads to false conclusions about the performance of the method, potentially compromising patient safety. The purpose of qualification, validation and verification is to generate reliable data for the products tested, resulting in the delivery of quality drug products to the patients. Therefore, the aim of this research is to emphasize the differences between verification and validation of analytical methods in the pharmaceutical industry

Development and validation of LC/MS/MS method for determination of mycotoxins

Mycotoxins (aflatoxins and ochratoxin A) are secondary toxic metabolites, that contaminate raw materials that are usually used in the preparation of products for human use. Presence of these contaminants in herbal drugs, used in the preparation of products for human use, can causes various acute and chronic impacts on human health. A novel LC/MS/MS method was developed and validated for determination of aflatoxins and ochratoxin A in cannabis flowers and extracts

Synergistic effects of terpenes and cannabinoids evaluated through antimicrobial activity

Cannabis sativa L. (Cannabaceae) is commonly used plant that is considered to have therapeutic potential. Extract obtained from cannabis plants contain cannabinoids as the main carriers of pharmacological effects and terpenes. The hypothesized synergistic interactions between cannabinoids and terpenes to obtain unique pharmacological effects have been investigated in several preclinical studies. But evidence from preclinical studies whether terpenes can act synergistic with cannabinoids remains unclear with insufficient data. Antimicrobial susceptibility testing of these compounds can be used for prediction of therapeutic outcome