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Concept: Active ingredient


The name “cosmeceuticals” is derived from “cosmetics and pharmaceuticals”, indicating that a specific product contains active ingredients. Marine algae have gained much importance in cosmeceutical product development due to their rich bioactive compounds. In the present review, marine algal compounds (phlorotannins, sulfated polysaccharides and tyrosinase inhibitors) have been discussed toward cosmeceutical application. In addition, atopic dermatitis and the possible role of matrix metalloproteinase (MMP) in skin-related diseases have been explored extensively for cosmeceutical products. The proper development of marine algae compounds will be helpful in cosmeceutical product development and in the development of the cosmeceutical industry.

Concepts: Algae, Cosmetics, Matrix metalloproteinase, Active ingredient, Food and Drug Administration, Seaweed, Algaculture, Cosmeceutical


In recent years, amorphous formulations and other special dosage forms of drug products have been investigated to achieve adequate solubility and disintegration. We have evaluated the distribution of crystalline and amorphous states of a drug product using Nanothermal analysis (Nano-TA) and Raman imaging methods. Compared to conventional differential scanning calorimetry, Nano-TA can be used to more rapidly characterize the crystalline and amorphous states of model formulations, including their ingredient distributions, without any sample preparation. In the current study, imaging maps obtained for specific model formulations were evaluated on the basis of their visual appearance and the physicochemical properties of the active pharmaceutical ingredient (API). In addition, the crystalline and amorphous states of the model formulations were distinguished by Raman mapping. Nano-TA was found to be useful for the characterization of crystalline and amorphous states of APIs and the distribution of other ingredients. This technology could be used to monitor the changes in crystalline forms of drug substances and dosage forms during processing. In addition, Nano-TA can be used to characterize amorphous states.

Concepts: Pharmacology, Physical chemistry, Materials science, Differential scanning calorimetry, Pharmaceutical drug, Glass transition, Active ingredient, Isothermal titration calorimetry


We report the detection and analysis of a suspected counterfeit sample of the anti-malarial medicine Metakelfin through developing Nitrogen-14 Nuclear Quadrupole Resonance (14N NQR) spectroscopy at a quantitative level. The sensitivity of quadrupolar parameters to the solid-state chemical environment of the molecule enables development of a technique capable of discrimination between the same pharmaceutical preparations made by different manufacturers. The 14N NQR signal returned by a tablet (or tablets) from a Metakelfin batch suspected to be counterfeit was compared with that acquired from a tablet(s) from a known-to-be-genuine batch from the same named manufacturer. Metakelfin contains two active pharmaceutical ingredients, sulfalene and pyrimethamine and NQR analysis revealed spectral differences for the sulfalene component indicative of differences in the processing history of the two batches. Furthermore, the NQR analysis provided quantitative information that the suspected counterfeit tablets contained only 43  3 % as much sulfalene as the genuine Metakelfin tablets. Conversely, conventional non-destructive analysis by FT-Raman and FT-NIR spectroscopies only achieved differentiation between batches, but no ascription. HPLC-UV analysis of the suspect tablets revealed a sulfalene content of 42  2 % of the labelled claim. The degree of agreement shows the promise of NQR as a means of the non-destructive identification and content-indicating first-stage analysis of counterfeit pharmaceuticals.

Concepts: Pharmacology, Medicine, Nuclear magnetic resonance, Pharmaceutical drug, Antimalarial drug, Active ingredient, Nuclear quadrupole resonance, Authentication


Salts of active pharmaceutical ingredients are often used to enhance solubility, dissolution rate, or take advantage of other improved solid-state properties. The selected form must be maintained during processing and shelf-life to ensure quality. We aimed to develop a model to quantify risk of disproportionation, where the salt dissociates back to the freebase form.

Concepts: Active ingredient, Solvation, Sulfate


This article examines the market entry of biosimilar low-molecular-weight heparins (LMWHs) in Europe by focusing on regulatory requirements, pricing, reimbursement, prescribing, and dispensing. The window for biosimilar LMWHs to enter the market is narrow on the supply side because of several factors. These include (1) regulatory requirements, including a quality dossier, clinical and nonclinical studies, pharmacodynamic and pharmacokinetic studies, immunogenicity studies, and a comparability exercise (but a reduction in clinical data requirements might be plausible in some cases); (2) prices of originator LMWHs are lower than those of other biologic products; (3) European prices of originator LMWHs are lower than those observed in the rest of the world; (4) research and development and manufacturing costs are substantial; (5) costs of active pharmaceutical ingredients have increased following the heparin contamination crisis; and (6) biosimilar LMWHs may be subjected to generic medicine pricing regulations. Furthermore, there are limited opportunities for biosimilar LMWHs on the demand side. This is because, although LMWHs have a large market volume in Europe, demand-side incentives for biosimilar LMWHs are largely absent, and the questions about interchangeability and substitution between originator and biosimilar LMWHs have yet to be fully resolved.

Concepts: Pharmacology, Law, Clinical research, Drug development, Low molecular weight heparin, Supply and demand, Active ingredient, Food and Drug Administration


Ion mobility spectrometry (IMS) served as a rapid, qualitative screening tool for the analysis of adulterated weight-loss products. We have previously shown that sibutramine extracted into methanol from dietary supplements can be detected at low levels (2ng) using a portable IMS spectrometer, and have adapted a similar method for the analysis of additional weight-loss product adulterants. An FDA collaborative study helped to define the limits for fluoxetine with a limit of detection of 2ng. We also evaluated more readily available, less toxic extraction solvents and found isopropanol and water were comparable to methanol. Isopropanol was favored over water for two reasons: (1) water increases the analysis time and (2) aqueous solutions were more susceptible to pH change, which affected the detection of sibutramine. In addition to sibutamine and fluoxetine, we surveyed 11 weight-loss adulterants; bumetanide, fenfluramine, furosemide, orlistat, phenolphthalein, phentermine, phenytoin, rimonabant, sertraline and two sibutramine analogs, desmethylsibutramine and didesmethylsibutramine, using portable and benchtop ion mobility spectrometers. Out of these 13 active pharmaceutical ingredients (APIs), portable and benchtop ion mobility spectrometers were capable of screening products for 10 of these APIs. The developed procedure was applied to two weight-loss dietary supplements using both portable and benchtop instruments. One product contained didesmethylsibutramine while the other contained didesmethylsibutramine and phenolphthalein.

Concepts: Mass spectrometry, Obesity, Ethanol, Chemistry, Pharmaceutical drug, Active ingredient, Monoamine oxidase inhibitor, Ion mobility spectrometry


Introduction: Many active pharmaceutical ingredients (APIs), in development and already on the market, show a limited and variable bioavailability mainly associated to inadequate biopharmaceutical properties such as aqueous solubility and dissolution rate. The latter is the main factor responsible for the limited, and sometimes inadequate, efficacy of many orally administered drugs, belonging to class II and IV of the Biopharmaceutics Classification System (BCS). Moreover, because of their low solubility, such drugs require high doses to be administered in order to obtain their pharmacological effect, increasing the side effect incidence. Areas covered: The present review reports the most common technological approaches intended to improve solubility and dissolution rate of BCS class II and IV drugs such as nanocrystals, solid dispersions, cyclodextrins and solid lipid nanoparticles. Particular attention will be focused on the use of inorganic matrices (lamellar anionic clays and mesoporous materials) as host for the delivery of poor soluble APIs (guest). Expert opinion: The employment of inorganic matrices for the realization of host-guest composites is a suitable strategy for the biopharmaceutical properties enhancement. This objective can be achieved without any modification of API chemical structure.

Concepts: Pharmacology, Drug, Solubility, Pharmaceutical drug, Biopharmaceutics Classification System, Bioavailability, Active ingredient, Solvation


The purpose of this work was to evaluate gas perfusion isothermal calorimetry (ITC) as a method to characterize the physicochemical changes of active pharmaceutical ingredients (APIs) intended to be formulated in pressurised metered dose inhalers (pMDIs) after exposure to a model propellant. Spray dried samples of beclomethasone dipropionate (BDP) and salbutamol sulphate (SS) were exposed to controlled quantities of 2H,3H-decafluoropentane (HPFP) to determine whether ITC could be used as a suitable analytical method for gathering data on the behavioural properties of the powders in real time. The crystallization kinetics of BDP and the physiochemical properties of SS were successfully characterized using ITC and supported by a variety of other analytical techniques. Correlations between real and model propellant systems were also established using hydrofluoroalkane (HFA-227) propellant. In summary, ITC was found to be suitable for gathering data on the crystallization kinetics of BDP and SS. In a wider context, this work will have implications on the use of ITC for stability testing of APIs in HFA-based pMDIs.

Concepts: Pharmacology, Asthma, Pharmaceutical drug, Active ingredient, Reaction rate, Salbutamol, Beclometasone dipropionate, Chemical physics


Nanotechnology receives a widespread application in semiconductor, manufacturing, and biotechnology industries [1]. Its biggest societal impact in pharmaceutical application is related to its use in design of nanomedicine with the aim to improve medical efficacy via resolving the poor drug bioavailability status. Pharmaceutical nanoparticles can be described as solid colloidal particles with sizes below 1000 nm [1-6]. Examples of nanocarrier are liposome, cocheates, polymeric micelle, dendrimer, nanosuspension, nanoemulsion, nanosphere and nanotube [4, 7-10]. The nanoparticles can be used to deliver polypeptides, proteins, nucleic acids, genes and vaccines [3]. Active pharmaceutical ingredients can be adsorbed, encapsulated or covalently attached to the surface/into the matrix of nanoparticles [1, 11-14]. Owing to small physical size and large specific surface area, they can improve the dissolution of poorly water-soluble drugs, enhance transcytosis across epithelial and endothelial barriers, enable drug targeting, enhance bioavailability, reduce dose and associated toxicity [1, 6, 14, 15]. Nanoparticles can enhance drug stability and efficacy, and enable sustained delivery [16, 17]. They can avoid or encounter rapid clearance by phagocytes thereby leading to prolonged or reduced drug circulation in the body, as a function of particle size and surface characteristics [8, 18, 19]. The nanoparticles can penetrate cells and target organs such as liver, spleen, lung, spinal cord and lymph. Its drug targeting element is mainly exploited in the treatment of solid tumors, cardiovascular diseases, and immunological diseases [15, 20-22]. Nonetheless, manufacturing of nanomedicine can be complex and additional hurdles are expected in the development for clinical usage. Spray drying is commonly used in the pharmaceutical industry to convert a liquid phase into a dry, solid powder. Both microparticles and nanoparticles can be produced/processed by means of spray drying technology. A thorough review of patents with reference to the value of spray drying technology in nanoproduct development and commercialization has been provided by Beck et al. (2012) and Patel et al. (2014) in the late issues of Recent Patents on Drug Delivery and Formulation [23,24]. Principally, the nanoparticles are obtainable via three approaches: i) spray drying solutions to obtain nanoparticles, ii) spray drying emulsions/dispersions to obtain nanoparticles and iii) spray drying pre-formed nanoparticles. The main challenges encountered by the existing spray drying or the latest nanospray drying technology are low production throughput, long production duration, and limited flexibility in processing operation when two or more reactive substances are required to be co-sprayed in situ, use of protein drugs that are prone to be lost via adsorption onto the processing device with time, and need of complex decoration of nanoparticles to enable drug targeting are concerned. Inferring from these shortfalls, it indicates that there is still an ample room for nanospray drying technology development in order to meet the therapeutic and commercial demands of the nanomedicine.

Concepts: Pharmacology, Drug, Nanotechnology, Colloid, Pharmaceutical drug, Active ingredient, Spray drying, BET theory


The efficacy of many hydrophobic bioactives (pharmaceuticals, supplements, and nutraceuticals) is limited due to their relatively low or highly variable bioavailability. Nanoemulsions consisting of small lipid droplets (r < 100 nm) dispersed in water can be designed to improve bioavailability. Areas covered: The major factors limiting the oral bioavailability of hydrophobic bioactive agents are highlighted: bioaccessibility, absorption and transformation. Two nanoemulsion-based approaches to control these processes and improve bioavailability are discussed: nanoemulsion delivery systems (NDS) and nanoemulsion excipient systems (NES). In NDS, hydrophobic bioactives are dissolved within the lipid phase of oil-in-water nanoemulsions. In NES, the bioactives are present within a conventional drug, supplement, or food, which is consumed with an oil-in-water nanoemulsion. Examples of NDS and NES utilization to improve bioactive bioavailability are given. Expert opinion: Considerable progress has been made in nanoemulsion design, fabrication, and testing. This knowledge facilitates the design of new formulations to improve the bioavailability of pharmaceuticals, supplements, and nutraceuticals. NDS and NES must be carefully designed based on the major factors limiting the bioavailability of specific bioactives. Research is still required to ensure these systems are commercially viable, and to demonstrate their safety and efficacy using animal and human feeding studies.

Concepts: Pharmacology, Surface tension, Pharmacokinetics, Design, Major, Biological activity, Bioavailability, Active ingredient