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The presence of pharmaceuticals in effluents, which are wastewater discharges from various sources, has emerged as a significant environmental concern in recent years. Among the various methods available to address this challenge, adsorption stands out as one of the most effective, both technically and economically. In this study, we investigate the potential of cross-linked chitosan (C-CHIT) as an adsorbent for sodium cromoglicate (CG) and sodium diclofenac (DF). Both CG and DF were found to spontaneously adsorb onto C-CHIT, a sorbent with a positively charged surface when dispersed in water (as confirmed by zeta potential measurements). The adsorption of these anionic drugs resulted in a change in the polarity of the surface charge. Thermodynamic analysis was conducted using a standard approach, wherein parameters from Redlich–Peterson and Frumkin isotherms at the low-concentration limit were utilized to calculate the enthalpy and entropy of adsorption. This analysis suggested that CG was more effectively adsorbed onto C-CHIT. Additionally, a novel approach was proposed in this study for adsorption under surface saturation conditions, which deviate from ideal solution conditions. Interestingly, thermodynamic data indicated a reversal of behavior, with DF being more effectively adsorbed by C-CHIT. This finding was supported by geometric parameters calculated using MarvinSketch 23.12, along with a more repulsive Frumkin's lateral interaction parameter for CG. [ABSTRACT FROM AUTHOR]

Understanding the transport mechanism is crucial for developing inhibitors that block allergen absorption and transport and prevent allergic reactions. However, the process of how beta-conglycinin, the primary allergen in soybeans, crosses the intestinal mucosal barrier remains unclear. The present study indicated that the transport of beta-conglycinin hydrolysates by IPEC-J2 monolayers occurred in a time- and quantity-dependent manner. The beta-conglycinin hydrolysates were absorbed into the cytoplasm of IPEC-J2 monolayers, while none were detected in the intercellular spaces. Furthermore, inhibitors such as methyl-beta-cyclodextrin (MβCD) and chlorpromazine (CPZ) significantly suppressed the absorption and transport of beta-conglycinin hydrolysates. Of particular interest, sodium cromoglycate (SCG) exhibited a quantity-dependent nonlinear suppression model on the absorption and transport of beta-conglycinin hydrolysates. In conclusion, beta-conglycinin crossed the IPEC-J2 monolayers through a transcellular pathway, involving both clathrin-mediated and caveolae-dependent endocytosis mechanisms. SCG suppressed the absorption and transport of beta-conglycinin hydrolysates by the IPEC-J2 monolayers by a quantity-dependent nonlinear model via clathrin-mediated and caveolae-dependent endocytosis. These findings provide promising targets for both the prevention and treatment of soybean allergies. [ABSTRACT FROM AUTHOR]

Khellin is the key furanocoumarin of Ammi visnaga L. (Lam.) that exhibits various biological properties. This unique natural product has inspired the discovery of two first-in-class drugs, amiodarone and sodium cromoglycate. A wide range of analytical methods were generated while translating khellin scaffold into clinically used drugs; however, they have never been reviewed and critically assessed. The present review aims to review and evaluate the analytical techniques for the natural products, khellin, visnagin, and their inspired drugs, amiodarone and sodium cromoglycate. High-performance liquid chromatography (HPLC) is the extensively used technique in most analytical methods reported for these compounds; however, other techniques including the fluorimetry, luminescence spectrophotometry, potentiometry, voltammetry, FT-Raman spectroscopy, and ELISA were also employed. The review will be helpful for further basic and translational research on furanochromone and related scaffolds. [ABSTRACT FROM AUTHOR]

Understanding the transport mechanism is crucial for developing inhibitors that block allergen absorption and transport and prevent allergic reactions. However, the process of how beta-conglycinin, the primary allergen in soybeans, crosses the intestinal mucosal barrier remains unclear. The present study indicated that the transport of beta-conglycinin hydrolysates by IPEC-J2 monolayers occurred in a time- and quantity-dependent manner. The beta-conglycinin hydrolysates were absorbed into the cytoplasm of IPEC-J2 monolayers, while none were detected in the intercellular spaces. Furthermore, inhibitors such as methyl-beta-cyclodextrin (MβCD) and chlorpromazine (CPZ) significantly suppressed the absorption and transport of beta-conglycinin hydrolysates. Of particular interest, sodium cromoglycate (SCG) exhibited a quantity-dependent nonlinear suppression model on the absorption and transport of beta-conglycinin hydrolysates. In conclusion, beta-conglycinin crossed the IPEC-J2 monolayers through a transcellular pathway, involving both clathrin-mediated and caveolae-dependent endocytosis mechanisms. SCG suppressed the absorption and transport of beta-conglycinin hydrolysates by the IPEC-J2 monolayers by a quantity-dependent nonlinear model via clathrin-mediated and caveolae-dependent endocytosis. These findings provide promising targets for both the prevention and treatment of soybean allergies.

Objective To discuss the effect of sodium cromoglycate (SCG) on the neural function and cognitive function in the rats with cerebral ischemic stroke (CIS), and to clarify its mechanism. Methods A total of 80 male SD rats were selected and 18 were randomly selected as sham operation group. The remaining rats were constructed the cerebral ischemia/reperfusion (I/R) injury models by thread embolization method. The 45 successful modeling rats were randomly divided into I/R group, I/R + low dose of SCG group, and I/R +high dose of SCG group (n=15) .At 24 h after modeling, the rats in I/R+low dose of SCG group and I/R +high dose of SCG group were intraperitoneally injected with 20 and 60 mg·kg－1 SCG for 2 weeks, respectively. The neurological scores of the rats in various groups were evaluated by modified neurological severity score (mNSS) criterion； the area of cerebral infarction was detected by using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining；the Y-maze experiment was used to detect the memory abilities of the rats in various groups；electrophysiological measurement was used to analyze the accurate reaction rate, accurate reaction time, and field excitatory postsynaptic potential (fEPSP) slopes of the rats in various groups；Golgi staining was used to detect the morphology of dendritic spines in dentate gyrus of hippocampus in brain tissue of the rats in various groups；immunofluorescence method was used to detect the numbers of 5-bromodeoxyuridine (BrdU) positive cells and the expression levels of doublecortin (DCX) protein in dentate gyrus of hippocampus in brain tissue of the rats in various groups； Western blotting method was used to detect the expression levels of brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), neurotrophin 3 (NT-3), and tyrosine kinase C receptor (TrkC) proteins in brain tissue of the rats in various groups. Results Compared with sham operation group, the neurological score and the cerebral infarction area of the rats in I/R group were increased (P<0.05), the accurate reaction rate was decreased (P<0.05), and the accurate reaction time was increased (P<0.05), the fEPSP slope and the density of dendritic spine was decreased (P<0.05), the number of BrdU positive cells in dentate gyrus of hippocampus in brain tissue and the expression level of DCX protein in hippocampus tissue had no significant differences (P>0.05), and the expression level of NT-3 protein in hippocampus tissue was increased (P<0.05), but the expression levels of BNDF, TrkB, and TrkC proteins had no significant differences (P>0.05) . Compared with I/R group, the neurological scores of the rats in I/R+high dose of SCG group was decreased (P<0.05), the infarction area was decreased (P<0.05), the accurate reaction rate was increased (P<0.05), the accurate reaction time was decreased (P<0.05), the fEPSP slope and the dendritic spine density were increased (P<0.05), the number of BrdU positive cells and the expression level of DCX protein in dentate gyrus of hippocampus in the brain tissue were increased (P<0.05), and the expression levels of BDNF, TrkB, NT-3, and TrkC proteins were significantly increased (P<0.05) . Conclusion SCG has the protective effect on the neurological and cognitive functions in the I/R model rats and its mechanism may be related to the increasing of the expressions of BDNF/TrkB and NT-3/TrkC signaling pathway related proteins and promoting the proliferation of the neurons. [ABSTRACT FROM AUTHOR]

Background. Mast cells are immune cells that mediate hypersensitivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been associated with different inflammatory conditions such as obesity and other adipose tissue disorders. Lipedema is a chronic disease characterized by an abnormal accumulation of adipose tissue on the legs and arms, pain, and other symptoms. Mast cells may play a role in the pathology of lipedema. Objective. Pilot study to determine levels of histamine and its metabolites in lipedema subcutaneous adipose tissue (SAT) biopsy samples, and to test sodium cromoglycate for the treatment of mast cells in women with lipedema. Methods. Biopsies from lipedema and control SAT were collected and analyzed histologically for the presence of mast cells. Mass spectrometry was used to measure the levels of histamine, a key marker of mast cells, and its metabolites in SAT in women with lipedema and controls, and after a group of women with lipedema were administered oral and topical doses of sodium cromoglycate for two weeks. Results. Histological examination of biopsies from lipedema patients confirmed the presence of mast cells. Metabolomic analysis revealed high levels of histamine and its metabolites in samples from women with lipedema compared to controls. Following a two-week treatment period, lipedema tissue samples exhibited reduced levels of histamine, suggesting a reduction of mast cell activity. Conclusion. Sodium cromoglycate has the ability to stabilize mast cells and reduce histamine levels in lipedema patients, which could be useful in lowering the symptoms of lipedema. [ABSTRACT FROM AUTHOR]

This article presents the results of studies of the levels of expression of the IL13R gene and the levels of expression of the molecular IL13R in the bronchi of control rats and rats with ovalbumin-induced asthma. The choice of these receptors is due to the great importance of these structures in the pathogenesis of allergic bronchial asthma. Biological materials of 64 Wistar rats were studied using real-time PCR and immunohistochemical methods. As a result of the studies, it was found that under conditions of asthma development in the tissues of the bronchi of rats, a pronounced expression of the IL13R genes, a significant expression of the molecular receptor for interleukin-13, occurs. In bronchi with an intramural ganglion (bifurcation zone), the level of IL13R gene expression and the level of expression of the IL13R molecular receptor were significantly higher than in tracheal samples without ganglia. Sodium cromoglycate, administered to rats 5 hours after the last inhalation of ovalbumin, led to a decrease in the mRNA content in the bronchi of animals compared to animals that did not receive mast cell stabilizer treatment. [ABSTRACT FROM AUTHOR]

Sodium hyaluronate (SHA) is an anti-inflammatory and protective agent against bronchoconstriction, and sodium cromoglicate (SCG) prevents exercise-induced bronchoconstriction and inflammation. Based on the pharmacological properties of both substances, this study aimed to develop a dry powder inhaler (DPI) of SHA alone and in combination with SCG. The target of the study was to develop flowable formulations without any surfactants by using the spray drying method. To obtain respirable SHA and SCG:SHA particles, variables of the spray dryer, such as inlet temperature, atomized air flow, and feed solution, were changed. The particles 1–8 μm in size were produced with high yield by spray drying and increasing the ethanol percentage of the feed solution (60%), which is the most remarkable parameter. After that, physicochemical characterizations were performed. The aerosol performance of DPI formulations prepared using lactose was evaluated using Handihaler® DPI. The fine particle fraction (FPF) was 36% for the SHA formulation, whereas it was 52 and 53% for SCG and SHA, respectively, in the SCG:SHA formulation. Consequently, both particles were produced reproducibly by spray drying, and inhaled SHA and SCG:SHA dry powder formulations were developed due to their high FPF and flowability with lactose. [ABSTRACT FROM AUTHOR]

IntroductionBullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease which mainly affects the elderly. It manifests as severe pruritus, urticarial plaques, and tense bullae and is associated with significant mortality. Therapy options for itch in BP patients are limited, mainly because the pathogenesis of itch in BP remains unclear. Sodium cromoglycate was commonly used in the past as an inhaled drug for the management of bronchial asthma and as an oral treatment for children with urticaria pigmentosa. In this study we sought to assess its efficacy in reducing BP associated itch.ObjectiveAssessing the efficacy of oral sodium cromoglycate in reducing BP-related pruritus after stabilization of disease activity.MethodsWe retrospectively reviewed the medical records of patients with a confirmed diagnosis of BP who were treated with sodium cromoglycate. Patient reported outcome measures (PROM) including: BPDAI pruritus, ABQOL and TABQOL, and BPDAI activity score were compared at two points in time: before commencing treatment with sodium cromoglycate or before commencing maximal dose of this treatment, and at least 4 weeks after treatment commencement.ResultsA total of 21 patients met the inclusion criteria. After at least 4 weeks of treatment with oral sodium cromoglycate BPDAI pruritus, ABQOL and TABQOL scores were statistically significantly decreased compared to the scores prior to treatment commencement, P < 0.000, P < 0.008, and P < 0.004, respectively.DiscussionOral treatment with sodium cromoglycate for the management of pruritus in BP patients may be beneficial, however, further prospective studies are required to better assess its efficacy.

The aim of this work was to study the effect of gas microbubbles on the production of particles suitable for inhalatory administration by a spray drying technology. An antiasthmatic model drug (sodium cromoglycate) was selected in order to evaluate the effect of different gases (air, CO2 and N2) and spray drying operating conditions on the particles aerosolization performance. To this end, gas supersaturated aqueous drug solutions were obtained in a pressurized vessel and then processed by spray drying. The process yield, morphology, size, bulk and tap densities, moisture content and aerosolization properties of the particles were evaluated. The presence of microbubbles in the spray drying feed led to powders with smaller mean geometric sizes than particles obtained without bubbles. The gas-water solubility emerged as a key parameter to obtain inhalatory particles with good aerosolization properties. High water-soluble gases led to bigger particles, while low soluble ones allow to produce smaller particles. The use of air (with an intermediate water solubility respect to CO2 and N2) and an adequate set of spray drying operating conditions allowed to obtain sodium cromoglycate particles with superior aerosolization properties than a commercial formulation. Overall, a novel, simple and low-cost method to produce inhalatory particles with excellent aerosolization properties was developed by supersaturating the spray drying liquid feed without using pore-forming agents during the production step, or carriers in the final formulation. [ABSTRACT FROM AUTHOR]

PURPOSE: This study aimed to assess the efficacy and safety of sodium cromoglycate with fluorometholone in patients with allergic conjunctivitis. METHODS: We conducted a single-arm phase IV open-label trial where fifty patients who received the eye drops were followed for 4 weeks. Treatment efficacy was assessed using the ocular itching score, conjunctival assessment score, total symptom and sign (TSS) score, and Visual Analog Scale (VAS). RESULTS: Patients who received sodium cromoglycate-fluorometholone eye drops experienced significant improvements in their ocular itching score (mean difference [MD]: 1.14, P = 0.001) and conjunctival redness score (MD: 1.18, P = 0.001). Statistically significant improvements in TSS and VAS were achieved in 78% of the patients reporting no conjunctivitis by the end of the study. The overall therapeutic response to the drug was as follows: 16% improved and 84% much improved. No serious adverse events were reported. CONCLUSION: Sodium cromoglycate with fluorometholone eye drops achieved 100% therapeutic response among patients with allergic conjunctivitis. The eye drops improve the ocular itching, and conjunctival irritation without serious adverse events. This combination appears effective and tolerable for treatment of allergic conjunctivitis. [ABSTRACT FROM AUTHOR]

Purpose. To study the effectiveness and tolerability of sodium cromoglycate (Uzbekistan) in the treatment of allergic conjunctivitis. Material and methods. 60 patients (120 eyes) with allergic conjunctivitis aged 18 to 60 years (28 men and 32 women), were divided into two homogeneous groups with similar clinical manifestations. The main group (30 patients), in addition to basic treatment, received instillations of sodium cromoglycate, 2 drops 4 times a day for 4 weeks. The control group (30 patients) received a foreign medication of the same group, instilled in the same way. Results. The patients of both groups revealed a comparable therapeutic effect. By the end of the treatment course, substantial positive changes were observed and the symptoms of allergic inflammation disappeared. The treatment effectiveness was 95.9 and 97.6 % in the main and the control groups, respectively. Conclusion. The use of domestic medication of the sodium cromoglycate group reduces the patients’ subjective complaints and helps achieve a maximum therapeutic effect at a price affordable by the patient and the clinic. No side effects or cases of intolerance to the drug of sodium cromoglycate group used have been revealed.

Background/Aims: Ulcerative colitis (UC) is a type of inflammatory bowel disease that mainly involves the colon. Thus far, glucocorticoids and amino-salicylate have been the main treatment. Methods: To assess drugs with fewer side effects, this study evaluated the effects of sodium cromoglycate (SCG) on acetic acid-induced UC in rats. The treatment groups included SCG receivers (50 and 100 mg/kg, intra-orally) and sulfasalazine (SSZ) receivers (100 mg/kg, intra-orally). The colonic mucosal injury was assessed by clinical, macroscopic, and histopathological examinations. Results: In the treatment groups with 50 and 100 mg/kg of SCG, the clinical activity score decreased to 2.67±0.18 and 1.73±0.21 (p

Hypoxia exposure often cause the increases of pulmonary arterial pressure (PAP). Studies reported that mast cells (MCs) participate in pulmonary vascular remodeling and promote the formation of chronic pulmonary hypertension. Current studies mainly focus on the change of MCs under chronic hypoxia, but few studies on the regulatory role and mechanism of MCs under acute hypoxia. Therefore, present study investigated the dynamic change of MCs in lung tissues under acute hypoxia and the role of MCs activation in the increasement of PAP. In our study, we established an experimental rat model of acute hypobaric hypoxia using a hypobaric chamber (simulated altitude of 7,000 m) and pretreated with MCs degranulation inhibitor sodium cromoglycate (SCG) to study the MCs changes under acute hypoxic exposure. We found that acute hypobaric hypoxia contributed to the increased quantity, activity, and degranulation of MCs and SCG pretreatment showed attenuated PAP elevation under acute hypoxia. Our findings implied that there is a possible mechanism of acute hypoxia cause rapid recruitment of MCs, activation, and explosive degranulation to release Tryptase, Chymase, IL-6, His, 5-HT, and Ang II, which further contributed to pulmonary microvascular contraction and increase in PAP. This work extends the knowledge about MCs, providing a potential profile of MCs as an alternative treatment for high-altitude pulmonary edema (HAPE)-related increased pulmonary artery pressure. [ABSTRACT FROM AUTHOR]

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Background: Recurrent cow's milk (CM) aspiration is often associated with gastroesophageal reflux in infants and toddlers and it seems to be implicated in the etiology of different inflammatory lung disorders. This study aimed to investigate ex vivo the impact of CM aspiration on human airways and whether treatment with beclomethasone dipropionate (BDP) or sodium cromoglycate (SCG) may prevent the potential CM-induced airway hyperresponsiveness (AHR). Methods: Human isolated bronchi were contracted by electrical field stimulation (EFS10Hz) to mimic the contractile tone induced by the parasympathetic activity and challenged with CM, fat/lactose-free CM, or human breast milk (HM). The effect of pre-treatment with beclomethasone dipropionate (BDP) and sodium cromoglycate (SCG) was also investigated on the AHR induced by CM. Results: After a 60 min-challenge with CM 1:10 v/v and fat/lactose-free CM 1:10 v/v, ASM significantly (P ​

Severe traumatic brain injury (TBI) results in significant functional disturbances in the hippocampus. Studies support that sodium cromoglycate (CG) induces neuroprotective effects. This study focused on investigating the effects of post-TBI subchronic administration of CG on hippocampal hyperexcitability and damage as well as on sensorimotor impairment in rats. In contrast to the control group (Sham+SS group), animals undergoing severe TBI (TBI+SS group) showed sensorimotor dysfunction over the experimental post-TBI period (day 2, 55%, p < 0.001; day 23, 39.5%, p < 0.001; day 30, 38.6%, p < 0.01). On day 30 post-TBI, TBI+SS group showed neuronal hyperexcitability (63.3%, p < 0.01). The hippocampus ipsilateral to the injury showed volume reduction (14.4%, p < 0.001) with a volume of damage of 0.15 ± 0.09 mm3. These changes were associated with neuronal loss in the dentate gyrus (ipsilateral, 33%, p < 0.05); hilus (ipsilateral, 77%, p < 0.001; contralateral, 51%, p < 0.001); Cornu Ammonis (CA)1 (ipsilateral, 40%, p < 0.01), and CA3 (ipsilateral, 52%, p < 0.001; contralateral, 34%, p < 0.01). Animals receiving subchronic treatment with CG (50 mg/kg, s.c. daily for 10 days) after TBI (TBI+CG group) displayed a sensorimotor dysfunction less evident than that of the TBI+SS group (p < 0.001). Their hippocampal excitability was similar to that of the Sham+SS group (p = 0.21). The TBI+CG group presented hippocampal volume reduction (12.7%, p = 0.94) and damage (0.10 ± 0.03 mm3, p > 0.99) similar to the TBI+SS group. However, their hippocampal neuronal preservation was similar to that of the Sham+SS group. These results indicate that CG represents an appropriate and novel pharmacological strategy to reduce the long-term sensorimotor impairment and hippocampal damage and hyperexcitability that result as consequences of severe TBI. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is one of the most common neurological diseases globally. Mast cells are known to be the main source of brain histamine, which is identified as being involved in seizure modulation. Sodium cromoglycate is a popular mast cell stabilizer and is proposed as the first line therapy in chronic asthma and systemic mastocytosis. Considering the importance of gestational period in brain formation and given the apparent role of the histaminergic system in developmental stages, the question arises as to whether gestational exposure to sodium cromoglycate can impact epileptic susceptibility in the offspring. OBJECTIVES: The aim of this study was to evaluate the effects of gestational exposure of sodium cromoglycate on pentylenetetrazole-induced epileptiform activities in the rat offspring. METHODS: Twelve pregnant Wistar rats were divided into 3 groups (n=4) including: two treatment groups which received intraperitoneal Sodium cromoglycate in doses of 25 and 50 mg/kg once daily at the last week of pregnancy, and the control group which only received Phosphate-buffered saline at the same amount (0.5 ml) and the same order. At postnatal day 12, eight male pups were selected from each group’s offspring. Anesthetized pups were transferred to stereotaxic frame and silver electrodes were implanted surgically over the brain cortex. After recovery, pups were placed into the recording chamber and pentylenetetrazole-induced epileptiform activities were measured. RESULTS: Electrographic data showed a decrement in seizure latency and increment in frequency/amplitude of the spikes in sodium cromoglycate groups in comparison to the control group (p

Background: Mast cells are immune cells that mediate hypersensi-tivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been associated with different inflammatory conditions such as obesity and other adipose tissue di-sorders. Lipedema is a chronic disease characterized by an abnormal accumulation of adipose tissue on the legs and arms, pain, and other symptoms. Mast cells may play a role in the pathology of lipedema., Objective: Pilot study to determine levels of histamine and its metabolites in lipedema subcutaneous adipose tissue (SAT) biopsy samples, and to test sodium cromoglycate for the treatment of mast cells in women with lipedema., Methods: Biopsies from lipedema and control SAT were collected and analyzed histologically for the presence of mast cells. Mass spec-trometry was used to measure the levels of histamine, a key marker of mast cells, and its metabolites in SAT in women with lipedema and controls, and after a group of women with lipedema were administered oral and topical doses of sodium cromoglycate for two weeks., Results: Histological examination of biopsies from lipedema patients confirmed the presence of mast cells. Metabolomic analysis revealed high levels of histamine and its metabolites in samples from women with lipedema compared to controls. Following a two-week treatment period, lipedema tissue samples exhibited reduced levels of histamine, suggesting a reduction of mast cell activity., Conclusion: Sodium cromoglycate has the ability to stabilize mast cells and reduce histamine levels in lipedema patients, which could be useful in lowering the symptoms of lipedema.

Abstract A simple technique to produce spray-dried porous particles for inhalatory administration was developed. The particles were produced using water as solvent, Sodium Cromoglycate as model drug and ammonium bicarbonate as pore forming agent. A central composite design was employed to study the influence of the: pore-forming agent concentration (in the drug aqueous solution fed to the spray dryer) and air inlet temperature on: process yield and powder properties. The powder particle size distribution, moisture content, densities and estimated aerodynamic diameters were studied. Also, particles morphology, hygroscopicity, surface area, in vitro aerosolization properties, dissolution rate and stability were evaluated for some selected samples. In addition, a novel friability test was proposed for mechanical resistance evaluation of the porous materials. A pore forming agent concentration of 1.25% (w/w) and an air inlet temperature of 170 °C were the optimal process parameters to produce porous particles suitable for inhalatory administration. The process yield was high and it was demonstrated that the particles were free of ammonium bicarbonate. The porous powder, obtained by a simple and scalable technique, exhibited low tap density, good stability even at long storage periods (12 months), appropriate mechanical resistance, high initial dissolution rate and excellent aerosolization performance. Graphical abstract Large porous inhalatory spray-dried particles obtained without using organic solvents and employing ammonium bicarbonate as pore forming agent. Unlabelled Image Highlights • Development of spray-dried inhalable porous particle without using organic solvents. • Cromoglycate porous particles with adequate in vitro aerosolization properties. • Appropriate long term stability of porous Cromoglycate inhalable particles. • Stable porous Cromoglycate inhalable particles even under mechanical stress. [ABSTRACT FROM AUTHOR]

Abstract For the first 40 years of the 20th century treatment for asthma occurred in response to an asthma attack. The treatments were given by injection or orally and included the adrenergic agonists adrenalin/epinephrine and ephedrine and a phosphodiesterase inhibitor theophylline. Epinephrine became available as an aerosol in 1930. After 1945, isoprenaline, a non-selective beta agonist, became available for oral use but it was most widely used by inhalation. Isoprenaline was short-acting with unwanted cardiac effects. More selective beta agonists, with a longer duration of action and fewer side-effects became available, including orciprenaline in 1967, salbutamol in 1969 and terbutaline in 1970. The inhaled steroid beclomethasone was available by 1972 and budesonide by 1982. Spirometry alone and in response to exercise was used to assess efficacy and duration of action of these drugs for the acute benefits of beta 2 agonists and the chronic benefits of corticosteroids. Early studies comparing oral and aerosol beta 2 agonists found equivalence in bronchodilator effect but the aerosol treatment was superior in preventing exercise-induced bronchoconstriction. Inhaled drugs are now widely used including the long-acting beta 2 agonists, salmeterol and formoterol, and the corticosteroids, fluticasone, ciclesonide, mometasone and triamcinolone, that act locally and have low systemic bio-availability. Repurposing drugs as inhaled therapies permitted direct delivery of low doses of drug to the site of action reducing the incidence of unwanted side-effects and permitting the prophylactic treatment of asthma. Graphical abstract Unwanted side-effects are greatest when beta 2 agonists and steroids are given by tablet or injection and least when they are given by inhalation. Unlabelled Image [ABSTRACT FROM AUTHOR]

Fluorometholone (FLM) and Sodium Cromoglycate (CMG) are co-formulated in ophthalmic preparation and showed marked instability under different conditions. Two specific, sensitive and precise stability-indicating chromatographic methods have been developed and validated for their determination in the presence of their degradation products and FLM impurity. Ten components were efficiently separated by them. The first method was HPTLC-spectrodensitometry, where the separation was achieved using silica gel 60 F254 HPTLC plates and developing system of ethyl acetate: methanol (9:1, v/v). The second method was a reversed phase HPLC associated with kinetic study of the degradation process and was successfully applied for determination of the studied compounds in spiked rabbit aqueous humor. The mobile phase was acetonitrile: methanol: 0.05 M potassium dihydrogenphosphate (0.1% trimethylamine); pH 2.5, adjusted with orthophosphoric acid (20: 30: 50, by volume). In both methods, the separated components were detected at 240 nm and system suitability was checked. Good correlation was obtained in the range of 0.10-24.00 and 0.20-48.00 µg band−1, for FLM and CMG by HPTLC. While for HPLC, the linearity ranges from 0.01-50.00 and 0.05-50.00 µg mL−1 for both drugs. The methods were applied in pharmaceutical formulation, where they were compared to the reported method with no significant difference. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the role of mast cells and mast cell-derived histamine in vincristine-induced neuropathic pain. Neuropathic pain was induced by administration of vincristine (100 μg/kg, i.p.) over a period of 10 days, with a break of 2 days, and pain behavioural estimations including pin prick, hot plate and acetone spray tests were performed to assess mechanical and heat hyperalgesia and cold allodynia, respectively, on days 0, 14 and 28. Mast cell stabilizer, sodium cromoglycate, H receptor antagonist promethazine and H receptor antagonist ranitidine were administered over a period of 12 days. Administration of vincristine resulted in significant development of heat and mechanical hyperalgesia as well as cold allodynia. Furthermore, the pain observed was markedly elevated on the 28th day in comparison to the 14th day. Administration of sodium cromoglycate, promethazine and ranitidine significantly reduced mechanical and heat hyperalgesia and cold allodynia. However, the pain-attenuating effects of ranitidine were significantly less as compared to sodium cromoglycate and promethazine, which suggests that H receptors play a more important role than H receptors in vincristine-induced neuropathic pain. It may be concluded that vincristine may degranulate mast cells to release inflammatory mediators, particularly histamine which may act through H (primarily H) and H receptors to induce neuropathic pain. [ABSTRACT FROM AUTHOR]

As requested by regulatory authorities, impurity profiling is an important issue of quality control. In this work, a simple and sensitive liquid chromatographic (LC) method compatible with mass spectrometry (MS) was developed to study related substances and degradation products in sodium cromoglycate drug substance and eye drops. The method used a Sunfire column (4.6 mm × 150 mm, 3.5 μm). Mobile phase A consisted of 10 mM ammonium formate and mobile phase B was acetonitrile. Linear gradient elution with a post-run time of 8 min was performed as follows: 0–30 min, 3% B to 50% B; 30–35 min, 50% B. The flow rate was set at 1.0 mL/min. Degradation experiments were performed to check the stability indicating properties of the developed method. Based on MS n spectral data and exact mass measurements, the chemical structures of 2 unknown impurities and 6 unknown degradation products were characterized, including impurity C listed in the European Pharmacopoeia as unknown structure. In addition, a plausible mechanism for the formation of the degradation products was also proposed. [ABSTRACT FROM AUTHOR]

Mast cells are immunological cells that are diversely distributed in different parts of the body. Their role in various pathological conditions such as hypersensitivity, atherosclerosis, pulmonary hypertension, and male infertility has been reported by different scientists. Apart from these, a number of studies have shown their important role in pathogenesis of neuropathic pain of diverse aetiology. They have been found to release active mediators, primarily histamine and serotonin on degranulation in response to different stimuli including chemical, nerve damage, toxin or disease-related conditions. The mast cells stabilizer has shown pain attenuating effects by preventing degranulation of mast cells. Similarly, compound 48/80 (first dose 200 μg/100 g and after 6-h interval, second dose of 500 μg/100 g) caused the degranulation of the accumulated endoneurial histamine and 5-HT antagonists have shown pain relieving effects by attenuating the effects of histamine and serotonin, respectively. On the other hand, the mast cell degranulator compound 48/80 has shown dual action depending on its time of administration. The present review discusses the critical role of mast cells in the generation and maintenance of neuropathic pain in experimental models. [ABSTRACT FROM AUTHOR]

Sodium cromoglycate (SC) is an antiasthmatic and antiallergenic drug commonly used for chronic inhalation therapy; however, many daily intakes are required due to the fast drug clearance from airways. For these reasons, SC polymeric particles for inhalatory administration with adequate aerosolization and mucoadhesive properties were designed to prolong the drug residence time in the site of action. Sodium carboxymethylcellulose (CMCNa), sodium hyaluronate, and sodium alginate were selected to co-process SC by spray drying. The influence of these polysaccharides on the spray drying process and powder quality was evaluated (among others, morphology, size, moisture content, hygroscopicity, flowability, densities, liquid sorption, and stability). In vitro aerosolization, drug release, and mucoadhesion performance were also studied. Particularly, a novel method to comparatively evaluate the interaction between formulations and mucin solution (mucoadhesion test) was proposed as a rapid methodology to measure adhesion properties of inhalable particles, being the results as indicative of clearance probability. Among all the studied formulations, the powder based on SC and CMCNa exhibited the best mucoadhesion and aerosolization performance, the highest process yield and adequate moisture content, hygroscopicity, and stability. SC-CMCNa formulation arose as a promising inhalatory system to reduce the daily intakes and to increase the patient compliance. [ABSTRACT FROM AUTHOR]