Active Pharmaceutical Ingredient Content Research Articles

A framework for the in silico assessment of the robustness of an MPC in a CDC line in function of process variability

The shift from batch manufacturing towards continuous manufacturing for the production of oral solid dosages requires the development and implementation of process models and process control. Previous work focused mainly on developing deterministic models for the investigated system. Furthermore, the in silico tuning and analysis of a control strategy are mostly done based on deterministic models. This deterministic approach could lead to wrong actions in diversion strategies and poor transferability of the controller performance if the system behaves differently than the deterministic model. This work introduces a framework that explicitly includes the process variability which is characteristic of powder handling processes and tests it on a novel continuous feeding-blending unit (i.e., the FE continuous processing system (CPS)), followed by a tablet press (i.e., the FE 55). It employs a stochastic model by allowing the model parameters to have a probability distribution. The performance of a model predictive control (MPC), steering the feed rate of the main excipient feeder to compensate for the feed rate deviations of the active pharmaceutical ingredient (API) feeder to keep the API concentration close to the desired value, is evaluated and the impact of process variability is assessed in a Monte Carlo (MC) analysis. Next to the process variability, a model for the prediction error of the chemometric model and realistic feed rate disturbances were included to increase the transferability of the results to the real system. The obtained results show that process variability is inherently present and that wrong conclusions can be drawn if it is not taken into account in the in silico analysis.

Development and Application of Control Concepts for Twin-Screw Wet Granulation in the ConsiGmaTM-25: Part 1 Granule Composition

Continuous manufacturing of pharmaceuticals offers several benefits, such as increased production efficiency, enhanced product quality control, and lower environmental footprint. To fully exploit these benefits, standard operation mode (production processes with no or minimal disturbance mitigation measures) should be supported by adopting novel quality-by-control (QbC) methodologies. The paper at hand is the first part of a study focused on developing QbC algorithms for optimizing twin-screw wet granulation in the industrial manufacturing line ConsiGmaTM-25, specifically addressing granule composition.This work relies on previously established process-analytical-technology (PAT) equipment for real-time monitoring of the granule composition, i.e., the active pharmaceutical ingredient (API) and liquid content in wet granules. The developed control platform integrates model-based process control algorithms that aim to keep the API- and liquid content at target values through real-time adjustments of the process parameters. Furthermore, the platform integrates a digital operator assistant, which aims to detect and classify granulation disturbances and provides messages and instructions for the plant operator.The present manuscript systematically outlines all design steps from the development phase in the simulation environment to the final real system application and validation. The control platform’s performance is demonstrated through selected test scenarios on the ConsiGmaTM-25 manufacturing line. The obtained results indicate improved disturbance robustness and an increase in intermediate/final product quality (compared to conventional operating modes): The process control algorithms successfully maintained the API- and liquid content at target values despite process disturbances. Furthermore, realistic disturbances (feeder, pump, and material) were accurately detected and classified by the digital assistant algorithm. The information was provided through a user interface, offering real-time support for plant personnel.

UV-Visible Spectroscopy: A Review on its Pharmaceutical and Bio-allied Sciences Applications

Abstract: Ultraviolet-Visible (UV-Vis) spectroscopy has emerged as a powerful analytical tool with diverse applications in pharmaceutical and bio-allied sciences. This article provides a comprehensive overview of the extensive utility of UV-Vis spectroscopy, emphasizing its pivotal role in characterizing and analyzing various compounds critical for drug development and bio-allied research. In the pharmaceutical sector, UV-Vis spectroscopy is a fundamental technique for quantifying the concentrations of active pharmaceutical ingredients (APIs) in formulations. Its non-destructive nature and high sensitivity make it an indispensable tool for quality control, ensuring the consistency and potency of pharmaceutical products. Furthermore, this technique has been employed in the study of drug-receptor interactions to elucidate the molecular mechanisms underlying therapeutic effects. In bio-allied applications, UV-Vis spectroscopy is used to analyze biomolecules like proteins, nucleic acids, and enzymes. This technique allows for the study of protein conformational changes, DNA structure, and enzymatic activity, offering crucial insights into fundamental biological processes. Additionally, UV-Vis spectroscopy aids in determining biomarker concentrations, assisting in the early diagnosis and monitoring of various diseases. This article also explores recent advancements in UV-Vis spectroscopy, including the integration of nanomaterials and computational approaches to enhance sensitivity and selectivity. Moreover, it discusses the potential of UV-Vis spectroscopy in emerging areas such as personalized medicine and point-of-care diagnostics. As technology continues to evolve, UV-Visible spectroscopy is poised to significantly contribute to the ever-expanding landscape of pharmaceutical and bio-related research.

The feasibility of Raman spectroscopy for accurate assessment of essential criteria in pharmaceutical industry by investigation of Metformin hydrochloride tableting process

AbstractAnalytical and real‐time technology in pharmaceutical manufacturing process is an important need to ensure that manufactured drugs are safe and effective. Raman spectroscopy is an emerging technique that is able to perform quantitative analysis nondestructively due to the molecular structure of many drugs. Monitoring the content uniformity and quantification of active pharmaceutical ingredient (API) in the tablet preparation process, without the assistance of solvent, is one of the key concerns in the formulation design in order to provide stable, pure, and homogenous finished products. In this study, we investigated the possibility of using Raman data as an analytical method to quantify API, the intra‐ and inter‐sample uniformity of content in the tableting process of Metformin hydrochloride tablets (C4H11N5.HCl). Analysis of all standard samples for prediction of API uniformity represents an acceptable accuracy and precision with a relative standard deviation of 2.55%. Further investigation of tablets regarding to relative Raman intensity of some characteristic peaks demonstrates the amount of API content with an accuracy of ≥96%. These values have a good adaption with pharmacopeia monograph. Findings reveal that the Raman method can be routinely utilized for quantifying API, controlling the content uniformity and the stability of drugs in different stages of manufacturing.

Determination of Concentration of Active Pharmaceutical Ingredients in Different Brands of Artemether/Lumefantrine Tablets Sold in the Pharmacies in Uganda

Substandard, counterfeit and falsified antimalarial agents are a big challenge to effective malaria elimination interventions mainly in developing countries. In low-and middle-income countries (LMICs), the quality of antimalarial agents inclusive of AL is affected by several factors including insufficient regulation porous borders and limited funds. This study therefore focused evaluation of quality of different brands of fixed dose artemether/ lumefantrine tablets sold in Ugandan Pharmacies. This was an experimental study conducted using AL tablets obtained from different pharmacies in the different cities of Uganda purchased using mystery shopper method. The samples were screened for quality using visual inspection, assessed different physical quality parameters like weight variation, friability, disintegration and dissolution and content assay tests were also done both for the brands from the pharmacies and their correspondent LTR. The assay test was done using HPLC technique USP method. The samples were considered substandard if the API content was outside 90-110% range of the label claim. Data was analysed using descriptive statistics and presented as means with standard deviations and frequencies. Out of the 16 brands in the study, 14 brands (88%) passed the artemether assay and two brands failed at 89.8% and 110.2% of declared artemether content. For Lumefantrine assay, out of the 16 brands in the study, 14 brands (88%) passed the Lumefantrine assay except two brands (12%). The presence of A/L brands that are unregistered and the total assay failure of the brands of 18% for the AL tablets purchased causes alarm and the total assay failure of the brands of 18% for the AL tablets purchased calls for NDA to intensify on its operations to find out the conformity of the pharmacies to selling only registered medicines. Keywords: Artemether Lumefantrine, Quality, Tablets

Hepatic-Accumulated Obeticholic Acid and Atorvastatin Self-Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic-Associated Fatty Liver Disease.

Exploration of medicines for efficient and safe management of metabolic-associated fatty liver disease (MAFLD) remains a challenge. Obeticholic acid (OCA), a selective farnesoid X receptor agonist, has been reported to ameliorate injury and inflammation in various liver diseases. However, its clinical application is mainly limited by poor solubility, low bioavailability, and potential side effects. Herein a hepatic-targeted nanodrugs composed of OCA and cholesterol-lowering atorvastatin (AHT) with an ideal active pharmaceutical ingredient (API) content for orally combined treatment of MAFLD is created. Such carrier-free nanocrystals (OCAHTs) are self-assembled, not only improving the stability in gastroenteric environments but also achieving hepatic accumulation through the bile acid transporter-mediated enterohepatic recycling process. Orally administrated OCAHT outperforms the simple combination of OCA and AHT in ameliorating of liver damage and inflammation in both acetaminophen-challenged mice and high-fat diet-induced MAFLD mice with less systematic toxicity. Importantly, OCAHT exerts profoundly reverse effects on MAFLD-associated molecular pathways, including impairing lipid metabolism, reducing inflammation, and enhancing the antioxidation response. This work not only provides a facile bile acid transporter-based strategy for hepatic-targeting drug delivery but also presents an efficient and safe full-API nanocrystal with which to facilitate the practical translation of nanomedicines against MAFLD.

The application of bioassay using Daphnia magna for the evaluation of hospital and pharmaceutical industry wastewater containing Active Pharmaceutical Ingredients (APIs) toxicity

Several groups of Contaminants of Emerging Concern (CECs) including Active Pharmaceutical Ingredients (APIs) can influence ecosystem even at low levels of exposure. The concentration of APIs often belongs to the class of micropollutants, so that toxicity tests should be developed using sensitive test organisms. In this research we developed a potential sensitive Daphnia magna to evaluate the toxicity of APIs-containing wastewater from the total of 7 hospitals and pharmaceutical industries in Greater Bandung, West Java, Indonesia. Physico-chemical parameters that were analyzed including pH, BOD5, COD, TSS, Total N, and Phenol, according to the Ministry of Environment Regulation No. 5/2014. To determine the LC50 values, the Whole Effluent Toxicity (WET) method was applied. The results showed that the maximum concentration of pH, BOD5, COD, TSS, Total N, and Phenol of the pharmaceutical industries WWTP effluents were 7.9, 293 mgL-1, 418 mgL-1, 37 mgL-1, 10.7 mgL-1, and 0.188 mgL-1, respectively. These values have fulfilled the effluent standards. However, based on the acute toxicity testing using WET method, it was found that the minimum LC50 value of those WWTP effluents was 6.51% or equal to the TUa value of 15.35. Based on the TUa toxicity class, this effluent was categorized to be high acute toxic (10 ≤ TUa < 100).

Photoactivated full-API nanodrug (FAND): harnessing transition metal complexes and MTH1 inhibitor for enhanced DNA damage in cancer cells.

The effectiveness of photodynamic therapy (PDT) has been greatly restricted by the hypoxic tumor microenvironment and the susceptible resistance of monotherapy. Although nanodrugs based on transition metal complexes capable of integrating PDT with photoactivated chemotherapy (PACT) have garnered tremendous attention as promising candidates for overcoming the above limitations, the therapeutic efficacy of these nanodrugs is still hampered by inadequate loading of active pharmaceutical ingredients (APIs) and the inherent ability of cancer cells to repair damaged DNA. Herein, we developed a photoactivated full-API nanodrug, Ru-T FAND, by one-step self-assembly of RuDPB and TH287. By virtue of its 100 wt% API content and favorable stability in water, the Ru-T FAND exhibited improved cellular uptake behavior and intracellular 1O2 generation. Attractively, the Ru-T FAND with triple anti-cancer modalities can photogenerate 1O2, photo-release DPB ligand and inhibit the repair of DNA damage, ultimately enhancing its phototherapeutic effect on cancer cells. Importantly, the uncaged DPB ligand from RuDPB emits red fluorescence, enabling real-time monitoring of the drug's absorption, distribution and efficacy. Collectively, the presented photoactivated Ru-T FANDs with multiple anti-cancer mechanisms will expand new horizons for the development of safe, efficient and synergistic tumor phototherapy strategies.

Antibiotic quality and use practices amongst dairy farmers and drug retailers in central Kenyan highlands

Understanding antibiotic use in dairy systems is critical to guide antimicrobial stewardship programs. We investigated antibiotic use practices in small-holder dairy farms, antibiotic quality, and antimicrobial resistance (AMR) awareness among veterinary drug retailers in a mixed farming community in the central Kenyan highlands. Data were collected from 248 dairy farms and 72 veterinary drug stores between February 2020 and October 2021. A scale was developed to measure knowledge about AMR and antibiotic use using item response theory, and regression models were used to evaluate factors associated with antibiotic use and AMR knowledge. The active pharmaceutical ingredient (API) content of 27 antibiotic samples was determined using high-performance liquid chromatography (HPLC). The presence and levels of 11 antibiotic residues in 108 milk samples collected from the study farms were also investigated using liquid chromatography tandem mass spectrometry (LC–MS/MS). Almost all farms (98.8%, n = 244) reported using antibiotics at least once in the last year, mostly for therapeutic reasons (35.5%). The most used antibiotics were tetracycline (30.6%), penicillin (16.7%), and sulfonamide (9.4%), either individually or in combination, and predominantly in the injectable form. Larger farm size (OR = 1.02, p < 0.001) and history of vaccination use (OR = 1.17, p < 0.001) were significantly associated with a higher frequency of antibiotic use. Drug retailers who advised on animal treatments had a significantly higher mean knowledge scores than those who only sold drugs. We found that 44.4% (12/27) of the tested antibiotics did not meet the United States Pharmacopeial test specifications (percentage of label claim). We detected nine antibiotics in milk, including oxytetracycline, sulfamethoxazole, and trimethoprim. However, only three samples exceeded the maximum residue limits set by the Codex Alimentarius Commission. Our findings indicate that antibiotics of poor quality are accessible and used in small-holder dairy systems, which can be found in milk. These results will aid future investigations on how to promote sustainable antibiotic use practices in dairy systems.

Quantitative analysis of cephalexin in solid dosage form by Raman spectroscopy and chemometric tools

Objective To use Raman Spectroscopy for qualitative and quantitative evaluation of pharmaceutical formulations of active pharmaceutical ingredient (API) of Cephalexin. Significance Raman Spectroscopy is a noninvasive, nondestructive, reliable and rapid detection technique used for various pharmaceutical drugs quantification. The present study explores the potential of Raman Spectroscopy for quantitative analysis of pharmaceutical drugs. Method For qualitative and quantitative analysis of Cephalexin API, various standard samples containing less and more concentration of API than commercial tablet was prepared. To study spectral differences, the mean plot of all the samples was prepared. For qualitative analysis, Principal Component Analysis (PCA) and for quantitative analysis Partial Least Square Regression analysis (PLSR) was used. Both of these are Multivariate data analysis techniques and give reliable results as published in previous literature. Results PCA model distinguished all the Raman Spectral data related to the various Cephalexin solid dosage formulations whereas the PLSR model was used to calculate the concentration of different unknown formulations. For the PLSR model, RMSEC and RMSEP were determined to be 3.3953 and 3.8972, respectively. The prediction efficiency of this built PLSR model was found to be very good with a goodness of the model value (R2) of 0.98. The PLSR model also predicted the concentrations of Cephalexin formulations in the blind or unknown sample. Conclusion These findings demonstrate that the Raman spectroscopy coupled to PLSR analysis could be regarded as a fast and effectively reliable tool for quantitative analysis of pharmaceutical drugs.

Towards rational design of API-poly(D, L-lactide-co-glycolide) based micro- and nanoparticles: The role of API-polymer compatibility prediction

Due to their unique properties, such as controlled drug release and improved bioavailability, polymeric microparticles and nanoparticles (MPs and NPs) have gained considerable interest in the pharmaceutical industry. Nevertheless, the high costs associated with biodegradable polymers and the active pharmaceutical ingredients (APIs) used for treating serious diseases, coupled with the vast number of API-polymer combinations, make the search for effective API-polymer MPs and NPs a costly and time-consuming process. In this work, the correlation between the compatibility of selected model APIs (i.e., ibuprofen, naproxen, paracetamol, and indomethacin) with poly(lactide-co-glycolide) (PLGA) derived from respective binary phase diagrams and characteristics of prepared MPs and NPs, such as the drug loading and solid-state properties, was investigated to probe the possibility of implementing the modeling of API-polymer thermodynamic and kinetic phase behavior as part of rational design of drug delivery systems based on MPs and NPs. API–PLGA-based MPs and NPs were formulated using an emulsion-solvent evaporation technique and were characterized for morphology, mean size, zeta potential, drug loading, and encapsulation efficiency. The solid-state properties of the encapsulated APIs were assessed using differential scanning calorimetry and X-ray powder diffraction. The evaluated compatibility was poor for all considered API–PLGA pairs, which is in alignment with the experimental results showing low drug loading in terms of amorphous API content. At the same time, drug loading of the studied APIs in terms of amorphous content was found to follow the same trend as their solubility in PLGA, indicating a clear correlation between API solubility in PLGA and achievable drug loading. These findings suggest that API-polymer phase behavior modeling and compatibility screening can be employed as an effective preformulation tool to estimate optimum initial API concentration for MP and NP preparation or, from a broader perspective, to tune or select polymeric carriers offering desired drug loading.

Microwave-Assisted Freeze-Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations.

Microwave-assisted freeze-drying (MFD) offers significant time savings compared to conventional freeze-drying (CFD). While a few studies have investigated the stability of biopharmaceuticals with low protein concentrations after MFD and storage, the impact of MFD on high-concentration monoclonal antibody (mAb) formulations remains unclear. In this study, we systematically examined the effect of protein concentration in MFD and assessed protein stability following MFD, CFD, and subsequent storage using seven protein formulations with various stabilizers and concentrations. We demonstrated that microwaves directly interact with the active pharmaceutical ingredient (API), leading to decreased physical stability, specifically aggregation, in high-concentration antibody formulations. Furthermore, typically used sugar:protein ratios from CFD were insufficient for stabilizing mAbs when applying microwaves. We identified the intermediate drying phase as the most critical for particle formation, and cooling the samples provided some protection for the mAb. Our findings suggest that MFD technology may not be universally applicable to formulations well tested in CFD and could be particularly beneficial for formulations with low API concentrations requiring substantial amounts of glass-forming excipients, such as vaccines and RNA-based products.

Liquid API feeding in pharmaceutical HME: Novel options in solid dosage manufacturing

Hot melt extrusion (HME) is a common unit operation. It is broadly applicable in the pharmaceutical industry and can be implemented in a continuous manufacturing line. However, the conventional way of active pharmaceutical ingredient (API) feeding with a pre-blend consisting of a powdered API and a polymer does not allow the flexibility and agility to adjust the process parameters, which is generally an essential part of continuous manufacturing. In addition, this method of API feeding may result in the segregation of the individual powder components or agglomeration of highly cohesive materials, leading to an inhomogeneous API content in the extrudates, especially at low doses. In this study, the universal applicability of liquid side feeding in pharmaceutical HME was demonstrated using various APIs suspended or dissolved in water and fed as suspension or undersaturated, supersaturated, and highly concentrated solutions into anterior parts of the extruder. The extrudates were characterized in terms of their API content, residual moisture content, and solid-state of the API embedded in the polymer. The results show that a uniform API content without major deviations can be obtained via this method. Furthermore, the residual moisture content of the extrudates was low enough to have no significant influence on further processing of the final dosage form. In summary, this advanced way of feeding allows an accurate, flexible, and agile feeding of APIs, facilitating the production of personalized final dosage forms and a novel option to link the manufacturing of the drug substance and the drug product.

Defining the data gap: What do we know about environmental exposure, hazards and risks of pharmaceuticals in the European aquatic environment?

Active pharmaceutical ingredients (APIs) and their transformation products inevitably enter waterways where they might cause adverse effects to aquatic organisms. Identifying the potential risks of APIs in the environment is therefore a goal and current strategic direction of environmental management described in the EU Strategic Approach to Pharmaceuticals in the Environment and the Green Deal. This is challenged by a paucity of monitoring and ecotoxicity data to adequately describe risks.In this study we analyze measured environmental concentrations (MECs) of APIs from 5933 sites in 25 European countries as documented in the EMPODAT database or collected by the German Environment Agency for the time period between 1997 and 2020. These data were compared with empirical data on the ecotoxicity of APIs from the U.S. EPA ECOTOX database. Although 1763 uniquely identifiable APIs are registered with the European Medicines Agency (EMA) for sale in the European Economic Area (EEA), only 312 (17.7%) of these are included in publicly available monitoring data, 36 (1.8%) compounds have sufficient ecotoxicological data to derive a PNEC, and only 27 (1.5%) compounds meet both the hazard and exposure data requirements required to to perform an environmental risk assessment according to EMA guidelines. Four of these compounds (14.8%) had a median risk quotient (RQ) > 1. Endocrine disruptors had the highest median RQ, with 7.0 and 5.6 for 17α-ethinyl-estradiol and 17β-estradiol respectively.A comparison of in-silico and empirical exposure data for 72 APIs demonstrated the high protectiveness of the current EMA guidelines, with predicted environmental concentrations (PECs) exceeding median MECs in 98.6% of cases, with a 100-fold median increase.This study describes the data shortfalls hindering an accurate assessment of the risk posed to European waterways by APIs, and identifies 68 APIs for prioritized inclusion in monitoring programs, and 66 APIs requiring ecotoxicity testing to fill current data gaps.

DEVELOPMENT OF THE BASICS OF SPRAY TECHNOLOGY FOR EXTERNAL APPLICATION

The basics of the technology for the preparation of a spray formulation for external use with analgesic and anti-inflammatory effects was developed. The quantitative content of active pharmaceutical ingredients and excipients was proposed. Comparative analysis of some indicators of the obtained spray with analogues on the pharmaceutical market of Ukraine was carried out. Material calculations allowed to estimate the amount of active pharmaceutical ingredients and excipients for the preparation of the spray and its packaging in bottles with a dropper in the laboratory. Based on the material calculations, a basic technological scheme for the production of the finished product was proposed. Economic calculations have been carried out, which demonstrate a high level of economic profitability of the development of such a preparation.

Soft Gelatine Capsules- Critical Quality Attributes of Chosen Excipients and Capsules Parameters Following the Quality by Design Concept

Soft gel capsules are a common form of medicine and food supplements. Quality, productivity and manufacturing time is crucial for producers during their development and industrial operations. To ensure the best quality of the product, it is necessary to know all critical process steps and parameters. The use of QbD elements is to ensure the quality of the drug product throughout its "life cycle". Quality by design (QbD) and its elements are described by the International Council of Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and in their guideline - chapter ICH Q8 (Pharmaceutical Development). One of the first steps in pharmaceutical product development is to prepare Quality Target Product Profile (QTPP) and analyse Critical Material Attributes (CMAs) and Critical Quality Attributes (CQAs) of excipients, active pharmaceutical ingredient (API) and final product. During this research, we investigated the CQAs of the excipients used in vitamin D3 soft gelatin capsules containing high doses of cholecalciferol, from 10 000 to 200 000 IU per capsule. We considered the viscosity of the gelatin mass, the effect of the addition of dye on the viscosity, and the impact of the colour of the gelatin mass on the active substance content in the final capsules. It was also investigated oily carriers (medium chain triglycerides and safflower oil) and antioxidants (alpha-tocopherol acetate vs butylhydroxytoluene), and their effect on API concentration in the capsule.

Determination of the Solid Content of Active Pharmaceutical Ingredient Powders in Suspension-Type Pharmaceutical Oral Jelly Using Time-Domain NMR.

This study determined the content of solid active pharmaceutical ingredient (API) powders dispersed in suspension-type pharmaceutical oral jellies using a low-field time-domain NMR (TD-NMR). The suspended jellies containing a designated API content were prepared and tested. Acetaminophen (APAP), indomethacin (IMC) and L-valine were used as test APIs. First, this study measured the T2 relaxation rate (the reciprocal of T2 relaxation time) by the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence, and then evaluated whether the API content could be determined by the acquired T2 relaxation rate. The T2 relaxation rate negatively correlated with API content to a certain extent, but their correlation was not sufficient for achieving a precise determination. Subsequently, the solid-echo pulse sequence measurement was adopted for this study. We found that NMR signals corresponding to solid components strongly correlated with API content. Thus, this method achieved a precise determination of API contents in suspended jellies. In addition, this study confirmed the effect of API particle size on the T2 relaxation rate by using an L-valine-containing jelly: the T2 relaxation rate became faster when a smaller API size was incorporated into the suspended jelly, while there was no difference in terms of the NMR signals measured by solid-echo pulse sequence. From these findings, TD-NMR could be a powerful tool for evaluating the API dispersion state in suspended oral jellies.

Inconsistency in the Composition of the Smoke of a Cannabis Cigarette as Smoking Progresses: Results, Mechanism, and Implications.

Background: The efficacy of cannabis treatment is determined by the active pharmaceutical ingredients (APIs) of the ingested composition. Despite smoking predominancy in cannabis treatment, very little is known regarding its yield and provision rate of cannabis APIs. Material and Methods: Ten experiments were performed, studying changes in APIs content during smoking, using a designated smoking machine. APIs content was evaluated via analysis of a cigarette's residuals and of the smoke composition; cannabinoid and terpene content were assessed. Results: Results demonstrated increased cannabinoid content in the cigarette sections closer to the mouth, as compared with those closer to the lit end. Similarly, cannabinoid content in the inhaled smoke increases as smoking progresses. Similar results are found for sesquiterpenes. Monoterpenes, having lower boiling points reach the smoke before the sesquiterpenes and cannabinoids do. Conclusion: A mechanism is proposed, including: (i) decarboxylation and evaporation of APIs adjacent to the lit end, (ii) transition of API vapors away from the hot zone, (iii) condensation of APIs in cigarette's sections closer to the mouth, and (iv) re-evaporation of APIs as the hot zone approaches, thereby reaching the smoke. Differences in the boiling points between the various APIs result in varying composition along the cigarette and in the inhaled smoke. The main implications are: (i) APIs delivery through smoking cannot be uniform, (ii) APIs amount per puff increases as smoking progresses, and (iii) terpenes are inhaled before the cannabinoids are. Thus, in addition to its known health-threatening hazards, smoking entails nonuniform provision of APIs, even within the same cigarette.

Qualitative and Quantitative Analysis of Azithromycin as Solid Dosage by Raman Spectroscopy.

Active pharmaceutical ingredients (APIs) and excipients are main drug constituents that ought to be identified qualitatively and quantitatively. Raman spectroscopy is aimed to be an efficient technique for pharmaceutical analysis in solid dosage forms. This technique can successfully be used in terms of qualitative and quantitative analysis of pharmaceutical drugs, their APIs, and excipients. In the proposed research, Raman spectroscopy has been employed to quantify Azithromycin based on its distinctive Raman spectral features by using commercially prepared formulations with altered API concentrations and excipients as well. Along with Raman spectroscopy, principal component analysis and partial least squares regression (PLSR), two multivariate data analysis techniques have been used for the identification and quantification of the API. For PLSR, goodness of fit of the model (R2) was found to be 0.99, whereas root mean square error of calibration was 0.46 and root mean square error of prediction was 2.42, which represent the performance of the model. This study highlights the efficiency of Raman spectroscopy in the field of pharmaceutics by preparing pharmaceutical formulations of any drug to quantify their API and excipients to compensate for the commercially prepared concentrations.

UV/Vis spectroscopy as an in-line monitoring tool for tablet content uniformity

Continuous manufacturing provides advantages compared to batch manufacturing and is increasingly gaining importance in the pharmaceutical industry. In particular, the implementation of tablet processes in continuous plants is an important part of current research. For this, in-line real-time monitoring of product quality through process analytical technology (PAT) tools is crucial. This study focuses on an in-line UV/Vis spectroscopy method for monitoring the active pharmaceutical ingredient (API) content in tablets. UV/Vis spectroscopy is particularly advantageous here, because it allows univariate data analysis without complex data processing. Experiments were conducted on a rotary tablet press. The tablets consisted of 7– 13 wt% theophylline monohydrate as API, lactose monohydrate and magnesium stearate. Two tablet production rates were investigated, 7200 and 20000 tablets per hour. The UV/Vis probe was mounted at the ejection position and measurements were taken on the tablet sidewall. Validation was according to ICH Q2 with respect to specificity, linearity, precision, accuracy and range. The specificity for this formulation was proven and linearity was sufficient with coefficients of determination of 0.9891 for the low throughput and 0.9936 for the high throughput. Repeatability and intermediate precision were investigated. Both were sufficient, indicated by coefficients of variations with a maximum of 6.46% and 6.34%, respectively. The accuracy was evaluated by mean percent recovery. This showed a higher accuracy at 20000 tablets per hour than 7200 tablets per hour. However, both throughputs demonstrate sufficient accuracy. Finally, UV/Vis spectroscopy is a promising alternative to the common NIR and Raman Spectroscopy.