Salbutamol Sulphate Research Articles

Exploring the influence of drug content on DPI powder properties and potential prediction of pulmonary drug deposition.

Based on dry powder inhaler (DPI) inhalation process, powder properties have a key influence on fluidization and deagglomeration behavior during aerosol generation. The aim of this study was to explore the influence of drug content on DPI powder properties and further reveal the correlations between powder properties and pulmonary deposition efficiency. Using salbutamol sulfate as a model drug, Lactohale® 100 as carrier, carrier-based binary mixtures were prepared at drug content from 0.5 to 10% (w/w), characterized with powder rheometer, faraday cage and Next Generation Impactor. It was demonstrated that drug content had a remarkable influence on powder behavior, and good correlations between powder properties and fine particle fraction (FPF) were established in drug content range 0.5-7%. A negative correlation between basic flowability energy and FPF, reflected a good flowability is beneficial for powder fluidization. Further properties characterization, including aeration ratio, permeability, pre-shear stress and aerodynamic specific charge, suggested a strong interaction is beneficial for powder deagglomeration. It's the first time that interaction indicator and flowability indicator were extracted with principal component analysis (PCA). In conclusion, drug content has a significant influence on powder properties. DPI formulations with a stronger interaction and meanwhile a better flowability are desirable for enhanced pulmonary drug delivery.

Spray-dried liposomes: A study of the effect of carbohydrate carrier and concentrations on liposome size and drug entrapment

Background and objective: Dry powder inhalation provide many promising features for drug delivery to the pulmonary system, such as localization of drug within the lungs, drug retention in the respiratory tract, and reduced systemic toxicities. This study aimed to prepare dry powders of liposomes containing salbutamol sulfate using spray drying and study the influence of carrier type and concentration on liposome size and drug entrapment following rehydration of liposomal powder. Methods: Ethanol based proliposomes technique was used to generate liposomes containing salbutamol sulfate. Carbohydrate carriers: lactose, trehalose, sucrose, and mannitol in 1:6 or 1:10 (w/w) lipid to carrier ratio were separately incorporated into liposome formulations and dried by Buchi Mini-SprayDryerB-290. The protective effects of the sugars were investigated in terms of product yield (%), volume median diameter and size distribution of liposomes and entrapment efficiency of the drug. Results: The product yield (%) of spray dried liposome formulations with carriers was in the following order; trehalose (94.02 ± 1.20%) > sucrose (69.91 ± 1.75%) > lactose (68.30 ± 1.14%) > mannitol (50.16±0.80%) for the 1:6 formulations. Depending on the carrier type and lipidto carrier ratio, the vesicle size of liposomes with lactose and mannitol increased significantly (P 0.05) compared to the control formulations (3.6µm ±0.24). For 1:10formulation, the vesicle size with mannitol (P <0.001) and sucrose (P <0.001) increased significantly. The drug entrapment efficiency using the 1:6 formulations was 20.74±1.78% for sucrose, 35.59±2.42% for trehalose, 67.21±1.89 % for lactose, and 80.84±3.64% for mannitol. Conclusion: Stable spray-dried liposomes were manufactured using sugars as carriers. The findings of this study have demonstrated the potential using of carbohydrate carriers to increase the physical stability of liposomes during the drying process, and trehalose can offer formulations with most desirable characteristics, while mannitol showed the least benefits.

Derivative Uv-Spectroscopic determination of theophylline, salbutamol sulfate and glycerylguaicolate in syrup mixture

This study aimed to determine theophylline, salbutamol sulfate and glycerylguaiacolate using ultraviolet spectrophotometry derivative. Research conducted in syrup was analyzed using zero crossing wavelength method. NaOH 0,1 N was selected as the solvent. Zero crossing wavelength of theophylline was 275 nm on the first derivative, salbutamol sulfate was 262 nm on the second derivative and glycerylguaiacolate was 243 nm on the third derivative. Results showed that the recovery of theophylline and glycerylguaiacolate were between 112,913%-118,353% and 116,129%-117,655%, respectively, while the relative standard deviation was between 1,090%-1,903% for theophylline and 1,013%-1,922% for glycerylguaiacolate. Limits of detection of theophylline and glycerylguaiacolate were 1,626 ppm and 6,375 ppm, respectively while limits of quantification were 4,927 ppm and 19,319 ppm. This results Thus, it was concluded that this method could be applied to determine theophylline and glycerylguaiacolate in syrup mixture.

Formulation and evaluation fast disintegrating film salbutamol sulfat using HPMC E15

The aim of the study was to formulate and evaluate Fast Disintegrating Film salbutamol sulfate with HPMC E15 polymer using a solvent casting method. FDF salbutamol sulphate preparations with variations oaaf HPMC E15 polymer concentration (F1 = 30%, F2 = 40%, F3 = 50% and F4 = 60%). Film of salbutamol sulphate was evaluated organoleptic, thickness, uniformity of weight, folding endurance, PH surface, moisture loss, moisture uptake and in vitro disintegration time. The result showed that film of salbutamol sulphate produce flexible and semi-transparent films. Evaluation results of thickness, weight, folding endurance, surface pH, moisture loss and moisture uptake and film disintegration time of all formulas met the requirements, except the uniformity of weight at F4, time of disintegration of F1, F2, F3 and F4 because high concentration of polymer and not added surfactant and superdisintegrant.

Effect of Lactose Pseudopolymorphic Transition on the Aerosolization Performance of Drug/Carrier Mixtures.

Physico-chemical properties of lactose are key factors in adhesive mixtures used as dry powder inhaler (DPI). Despite the abundant literature on this topic, the effect of the polymorphism and pseudo-polymorphism of lactose has been seldom investigated and discussed although often lactose used in DPI is subjected to unit operations, which may alter its solid-state properties. Here, we studied the aerosolization performance of salbutamol sulphate (SS) or budesonide (BUD) formulations by investigating the effect of lactose pseudopolymorphism in ternary (coarse lactose/fine lactose/drug) and binary (coarse lactose/drug) mixtures. An improvement of the aerosolization performance of SS formulations with the increase of the amount of fine micronized lactose up to 30% (fine particle fraction (FPF) = 57%) was observed. Micronized lactose contained hygroscopic anhydrous α-lactose, which converted to α-lactose monohydrate at ambient conditions. This implied that the positive effect of fines on the aerosolization performance decreased and eventually disappeared with the formulation aging. Positive effect on SS deposition was observed also with binary mixtures with anhydrous lactose, whereas the opposite occurred with budesonide-containing formulations. The collected data demonstrated the crucial role of the carrier crystal form on the positive effect of fines on the deposition.

Lectin coupled liposomes for pulmonary delivery of salbutamol sulphate for better management of asthma: Formulation development using QbD approach

Lectin coupled liposomes for pulmonary delivery of salbutamol sulphate for better management of asthma: Formulation development using QbD approach

Association of human serum paraoxonase-1 with some respiratory drugs.

In this study, we investigated the effects of certainrespiratory drugs, which are mainly usedon human serum paraoxonase-1 (hPON1; EC 3.1.8.1). hPON1 was purified from human serum, with 354.91 fold and 45% yield by using two simple step procedures including, first, ammonium sulfate precipitation, then, Sepharose-4B-l-tyrosine-1-naphthylamine hydrophobic interaction chromatography. SDS-polyacrylamide gel electrophoresis showed a single protein band belongingto hPON1 with 43 kDa. All the pharmaceutical compounds inhibited the PON1 enzyme highly at the micromolar level. The obtained IC50 values for nine different pharmaceutics ranged from 0.219 μM (salbutamol sulfate) to 67.205 μM (montelukast sodium). So, all drugs couldbe considered as potent hPON1 inhibitors. Ki values and inhibition types were determined by Lineweaver-Burk graphs. While varenicline tartrate and moxifloxacin hydrochloride inhibited the enzyme in a noncompetitive manner, others inhibited it in a mixed manner.

DEVELOPMENT AND VALIDATION OF A SIMPLE UV SPECTROPHOTOMETRIC METHOD FOR THE ESTIMATION OF SALBUTAMOL SULPHATE FROM PHARMACEUTICAL FORMULATIONS

Objective: The present study was undertaken to develop a rapid, simple, specific and economic ultraviolet (UV) spectrophotometric method for estimating the Salbutamol Sulphate (SS) in pharmaceutical formulations.&#x0D; Methods: The analysis was performed at λ max 276 nm using Sorenson’s isotonic phosphate buffer pH 7 (SIPB pH 7) as blank/diluent. The method was validated by following the analytical performance parameters as suggested by International Conference on Harmonization (ICH) which included accuracy, precision, linearity.&#x0D; Results: The drug follows the beer’s lambert’s law in the concentration range of 12.5-37.5μg/ml and exhibited good correlation coefficient (0.9997) and excellent mean recovery. Percentage RSD for precision and accuracy of the method was found to be less than 2%. This method was successfully applied for the determination of the Salbutamol Sulphate in commercial brands of Indian market and the results were in good agreement with the label claims. The developed method was suitable and specific to the analysis of Salbutamol Sulphate even in the presence of common excipients.&#x0D; Conclusion: The obtained results proved that the validated method can be employed for the routine analysis of Salbutamol Sulphate in bulk as well as in the commercial formulations.

Impact of drug particle shape on permeability and cellular uptake in the lung

The generation of inhalable sized particles (1–5 μm) usually involves a particle-processing step; most commonly milling but spray drying has shown to be a suitable alternative. Besides particle size, processing may affect other particle properties, like shape and solid-state. For example, spray drying of salbutamol sulphate leads to spherical shaped predominantly amorphous particles whereas jet milling frequently maintains the irregular shape and the crystallinity of the raw material. The aim of the present study was to investigate whether particle properties, especially shape, change the biological action of the inhaled particles as well. Therefore, highly water soluble salbutamol sulphate and poorly water soluble budesonide were compared regarding dissolution, permeation and preferential uptake by epithelial cells compared to macrophages after jet milling and spray drying.For both drugs the spray dried, predominantly amorphous, particles resulted in lower respirable fractions, but higher permeability and cell uptake rates compared to the needle shaped, predominantly crystalline particles. The distinct particle properties did not affect the dissolution behaviour of salbutamol sulphate. In turn for drugs with lower solubility (budesonide), spray dried particles dissolved slower compared to jet milled particles. Preferential uptake by macrophages was higher for spray dried particles, suggesting that processing may improve targeted delivery. The comparison between murine cell lines and human monocyte derived macrophages primary cells showed similar trends in rate and preference of particle uptake.

Spectrophotometric Assay of Salbutamol Sulphate in Pharmaceutical Preparations by Coupling with Diazotized ρ-bromoaniline

In this research, salbutamol sulphate (SAS) has been determined by a simple, rapid and sensitive spectrophotometric method. Salbutamol sulphate in this method is based on the coupling of SAS with diazotized ρ- bromoaniline reagent in alkaline medium of Triton X-100 (Tx) to form an orange azo dye which is stable and water-soluble. The azo dye is exhibiting maximum absorption at 441 nm. A 10 - 800 µg of SAS is obeyed of Beer's law in a final volume of 20 ml, i.e., 0.5- 40 ppm with ε, the molar absorptivity of 48558 L.mol-1.cm-1 and Sandell's sensitivity index of 0.01188 µg.cm-2. This new method does not need solvent extraction or temperature control which is well applied to determine SAS in different types of pharmaceutical preparations.

On the Study of Sorption in the Chiral Separation of the Enantiomers of Salbutamol and Salmeterol by Supercritical Fluid Chromatography

The studied conditions of supercritical fluid chiral chromatography of salbutamol and salbutamol sulfate allowed to assumethe possibility of ionic interactions in the process of separation of enantiomers. It is shown that the structure of the hydrocarbon radical of 1- (4-hydroxy-3- (hydroxymethyl) phenyl) -2-aminoethanol associated with the chiral fragment, and, consequently, the physicochemical characteristics of the substance molecule, such as the number of hydrogen donors and acceptors polar surface, significantly affect the ability to communicate with the sorbent selectors under conditions of supercritical fluid chromatography

Assessment of the Air Quality Health Index (AQHI) and four alternate AQHI-Plus amendments for wildfire seasons in British Columbia.

Wildfire smoke is an important source of air pollution associated with a range of cardiopulmonary health conditions. The Air Quality Health Index (AQHI) is the most widely used tool in Canada to communicate with the public about air pollution, but it may not adequately reflect health risks from wildfire smoke. The objective of this study was to evaluate the ability of the AQHI and four alternate AQHI-Plus amendments to predict adverse population health effects from wildfire smoke. The maximum 1-h values of the AQHI and the four amendments were calculated for each 48-h period of the wildfire seasons from 2010 to 2017 for 32 health units in British Columbia. Generalized Poisson models were used to estimate the association between these values and daily counts of five health outcomes: all-cause mortality; physician visits for all circulatory causes; visits for all respiratory causes, including asthma; asthma-specific visits; and dispensations of salbutamol sulfate (i.e., Ventolin®). Model fit was evaluated with the Akaike information criterion. The AQHI and the four amendments were all associated with all five health outcomes. The AQHI exhibited best fit to the all-cause mortality and circulatory physician visits during all wildfire seasons, while the 1-h PM2.5Only AQHI-Plus exhibited best fit to the asthma-related outcomes during all wildfire seasons. Individuals with common respiratory conditions such as asthma and chronic obstructive pulmonary disease are particularly susceptible to wildfire smoke. As such, the 1-h PM2.5Only AQHI-Plus amendment was recommended for communicating about potential health effects of air quality during wildfire seasons in BC.

Screening and greenness profiling of oxidative-coupling and electrophilic aromatic substitution reactions for determination of three phenolic drugs

In this study, we screened oxidative-coupling and electrophilic aromatic substitution reactions for developing simple, economic, and environment-friendly spectrophotometric methods for three widely prescribed phenolic drugs; salbutamol sulfate (SLB), terbutaline sulfate (TBT), and thymol (THY). Methods IA and IB rely on the oxidative-coupling reaction of SLB and TBT with p-phenylenediamine in the presence of an oxidizing agent in carbonate buffer while Method II depends on electrophilic aromatic substitution reaction of THY with sodium nitroprusside/hydroxylamine hydrochloride in phosphate buffer (pH 12.0). Different experimental conditions controlling the derivatization reactions were optimized and the reaction products were quantified at 552, 400, and 700 nm, for SLB, TBT, and THY, respectively. Beer's-Lambert law was obeyed over wide linearity ranges with limits of detection from 6 to 126 ppb for the target analytes. Furthermore, the developed methods were validated as per ICH guidance. In addition, profiling of the methods greenness was conducted by adopting the National Environmental Methods Index and the analytical eco-scale score approaches. The two approaches elucidated the excellent greenness of the developed methods which emphasized their applicability for quality control analysis. Thus, the developed methods were efficaciously used for the determination of the three drugs in different dosage forms with excellent accuracy, where % found ranged from 98.86%–102.77%, and no interference from additives in the formulations.

Adverse effects of respiratory disease medicaments and tooth brushing on teeth: A scanning electron microscopy, X-ray fluorescence and infrared spectroscopy study.

The present study aims to evaluate the effect of brushing with fluoride dentifrice on teeth severely affected by erosion due to respiratory medicaments. Enamel (n = 50) and dentin (n = 50) bovine specimens were prepared and treated with artificial saliva (S-control), acebrofilin hydrochloride (AC), ambroxol hydrochloride (AM), bromhexine hydrochloride (BR), and salbutamol sulfate (SS) and subjected to cycles of demineralization (immersing in 3 mL, 1 min, three times a day at intervals of 1 hr, for 5 days) followed by remineralization (saliva, 37°C, 1 hr). Simulated brushing with fluoridated toothpaste was performed using 810 strokes in a reciprocal-action brushing simulator. Scanning electron microscopy, micro energy dispersive X-ray fluorescence (μ-EDXRF) spectroscopy and attenuated total reflection Fourier transform infrared (ATR FTIR) spectroscopy were then performed. μ-EDXRF images showed extensive erosion after treatment with all medicaments. SEM images showed enamel erosion in order SS > BR > AC = AM > S after brushing and fluoridation. FTIR results were in agreement. In case of dentin, μ-EDXRF measurements showed significant difference in mineral content (percent weight of calcium and phosphate) in SS + brushing + fluoridation treated enamel compared to control, while μ-EDXRF images showed erosive effects in the order SS > AM>BR > AC = S post brushing + fluoridation. SEM images showed erosion in the order SS > AM = BR > AC > S post brushing + fluoridation. Again, FTIR multivariate results were in agreement. Overall, our study shows that proper oral care is critical when taking certain medication. The study also demonstrates the possible use of FTIR for rapid clinical monitoring of tooth erosion in clinics.

Bilinear and trilinear algorithms utilizing full and selected variables for resolution and quantitation of four components with overlapped spectral signals in bulk and syrup dosage form.

Spectrophotometric-assisted chemometric techniques are beneficial for resolving spectral overlapping and are considered comparable to traditional chromatographic methods. In this work, different chemometric approaches were applied for simultaneous determination of Bromhexine HCl (BRHX), Guaifenesin (GUA) and Salbutamol sulphate (SALB) in the presence of Guaiacol (GUAIA), without any prior separation. Two-way and three-way techniques were applied. The resolving power of genetic algorithm (GA-PLS), trilinear partial least square (N-PLS) and multivariate curve resolution (MCR-ALS) were investigated. A set of 17 synthetic samples in the concentration range 10.0-30.0 μg/mL of BRHX, GUA and SALB and 6.0-10.0 μg/mL of GUAIA were used in the construction of the calibration models. Commercially available syrup dosage form was successfully analyzed by the developed methods without interference from formulation additives. The developed models were evaluated through calculation of root mean squared error of prediction (RMSEP), the obtained values were 0.263, 0.419 and 0.342 for BRHX, 0.254, 0.318 and 0.503 for GUA and 0.298, 0.268 and 0.302 for SALB using N-PLS, MCR-ALS and GA-PLS, respectively. The resolving power of the developed models was emphasized through comparison with a reported HPLC method, where no significant difference was found regarding both accuracy and precision.

Lung delivery of nanoliposomal salbutamol sulfate dry powder inhalation for facilitated asthma therapy

The motive behind present work was to discover a solution for overcoming the problems allied with a deprived oral bioavailability of salbutamol sulfate (SS) due to its first pass hepatic metabolism, shorter half-life, and systemic toxicity at high doses. Pulmonary delivery provides an alternative route of administration to avoid hepatic metabolism of SS, moreover facilitated diffusion and prolonged retention can be achieved by incorporation into liposomes. Liposomes were prepared by thin film hydration technique using 32 full factorial design and formulation was optimized based on the vesicle size and percent drug entrapment (PDE) of liposomes. Optimized liposomal formulation exhibited an average size of about 167.2 ± 0.170 nm, with 80.68 ± 0.74% drug entrapment, and 9.74 ± 1.10 mV zeta potential. The liposomal dispersion was then spray dried and further characterized for in-vitro aerosol performance using Andersen Cascade Impactor. Optimized liposomal formulation revealed prolonged in-vitro drug release of more than 90% up to 14 h following Higuchi’s controlled release model. Thus, the proposed new-fangled liposomal formulation would be a propitious alternative to conventional therapy for efficient and methodical treatment of asthma and alike respiratory ailments.

Effect of Albuterol Premedication vs Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies

Tonsillectomy is a common pediatric procedure for the treatment of sleep-disordered breathing and chronic tonsillitis. Up to half of children having this procedure experience a perioperative respiratory adverse event. To determine whether inhaled albuterol sulfate (salbutamol sulfate) premedication decreases the risk of perioperative respiratory adverse events in children undergoing anesthesia for tonsillectomy. A randomized, triple-blind, placebo-controlled trial (the Reducing Anesthetic Complications in Children Undergoing Tonsillectomies [REACT] trial) was conducted at Perth Children's Hospital (formerly Princess Margaret Hospital for Children), the only tertiary pediatric hospital in Western Australia. Participants included 484 children aged 0 to 8 years who were undergoing anesthesia for tonsillectomy. The study was conducted between July 15, 2014, and May 18, 2017. Participants were randomized to receive either albuterol (2 actuations, 200 μg) or placebo before their surgery. Occurrence of perioperative respiratory adverse events (bronchospasm, laryngospasm, airway obstruction, desaturation, coughing, and stridor) until discharge from the postanesthesia care unit. Of 484 randomized children (median [range] age, 5.6 [1.6-8.9] years; 285 [58.9%] boys), 479 data sets were available for intention-to-treat analysis. Perioperative respiratory adverse events occurred in 67 of 241 children (27.8%) receiving albuterol and 114 of 238 children (47.9%) receiving placebo. After adjusting for age, type of airway device, and severity of obstructive sleep apnea in a binary logistic regression model, the likelihood of perioperative respiratory adverse events remained significantly higher in the placebo group compared with the albuterol group (odds ratio, 2.8; 95% CI, 1.9-4.2; P < .001). Significant differences were seen in children receiving placebo vs albuterol in laryngospasm (28 [11.8%] vs 12 [5.0%]; P = .009), coughing (79 [33.2%] vs 27 [11.2%]; P < .001), and oxygen desaturation (54 [22.7%] vs 36 [14.9%]; P = .03). Albuterol premedication administered before tonsillectomy under general anesthesia in young children resulted in a clinically significant reduction in rates of perioperative respiratory adverse events compared with the rates in children who received placebo. Premedication with albuterol should be considered for children undergoing tonsillectomy. Australian New Zealand Clinical Trials Registry identifier: ACTRN12614000739617.

Comparison between the next generation impactor and the twin glass impinge as model pulmonary drug delivery devices

Background and objective: The British Pharmacopoeia contains four apparatus for testing inhalers. Two of these are the next generation impactor, and the twin glass impinge which differs in their use. The next generation impactor apparatus should ideally have at least five stages; even though the twin glass impinge has only two stages, it is still listed in the British Pharmacopoeia. The next generation impactor is more accurate, reliable and sophisticated than the twin glass impinger. This study gives a detailed comparison of the two pieces of equipment. Methods: Carriers including mannitol, lactose monohydrate, trehalose and sucrose with active pharmaceutical ingredient; salbutamol sulphate were delivered by dry powder inhaler using the next generation impactor and twin glass impinger at a constant flow rate of 60L/min. Results: The twin glass impinge respirable fractions of the powders were higher than the next generation impactor for each carrier. As expected, mannitol powder had the lowest percentage remaining in the capsule compared to lactose monohydrate, trehalose and sucrose had the greatest percentage remaining for both inhaler devices. Conclusion: Even though both apparatus are important for in-vitro studies of drug delivery into the lungs using inhaler devices, the next generation impactor is better suited when a specific size range is required. The twin glass impinger is useful for simple inhaler testing, and the inclusion within the British Pharmacopoeia is justified.

Clinical effect of montelukast combined with budesonide in the treatment of children with cough variant asthma

Objective To explore the curative effect of montelukast combined with budesonide in the treatment of cough variant asthma in children, to provide guidance for clinical practice. Methods From March 2015 to March 2017, 90 children with cough variant asthma in the People's Hospital of Yanggu County were randomly divided into observation group(n=45) and control group(n=45) according to the digital table.The observation group was given budesonide combined with montelukast, while the control group was given budesonide combined with salbutamol sulfate.All patients were followed up for 3 months.The curative effect, cough relief time, cough disappearance time, incidence rate of adverse reaction and recurrence rate were compared between the two groups. Results The total effective rate of the observation group(95.56%) was significantly higher than 77.78% of the control group(P 0.05). The recurrence rate of the observation group (4.44%) was significantly lower than 17.78% of the control group(P<0.05). Conclusion It is feasible to treat cough variant asthma in children with montelukast combined with budesonide, and it is helpful to reduce recurrence. Key words: Montelukast; Budesonide; Children; Asthma, Variability; Salbutamol Sulfate

Unexpected separate elution of cation and anion of an ammonium salt in supercritical fluid chromatography

Amines are frequently used as additives in supercritical fluid chromatography (SFC). They allow eluting basic analytes with reasonable retention times and less distorted peak shapes. Since amines are chemically active compounds, their introduction into SFC mobile phase always raises a question on whether they can react with analytes or mobile phase constituents and, if so, can it affect chromatography separation. Primary and secondary amines are known to react with carbon dioxide, also all amines, being bases, can interact with CO2-alcohol mixtures which are known to be slightly acidic. In this work, we report a case of separate elution of an ammonium salt, salbutamol sulfate, anion and cation in SFC. Retention time of a peak which molecular mass registered by mass-spectrometry in ES(-) mode corresponds to HSO4− differs substantially from the retention time of a peak corresponding to salbutamol [M+H] registered in ES(+) regime. Moreover, sulfate anion retention time depends both on amine additive type and concentration whereas salbutamol retention time doesn’t. Similar effect is observed on other columns as well as with other ammonium salts. We suppose that such behavior is caused by the exchange chemical reaction happening between ammonium salt analyte and amine additive. An additive converts a salt into a free base form and turns into a salt form itself. If this hypothesis is true, it might be important to take the possibility of such interactions into account during preparative SFC work since the compound injected might not be equivalent to a compound eluted.