Crystallization engineering techniques for developing a novel dry powder inhaler formulation for ibuprofen

The technique of producing inhalable particles (<5&#956;m) for dry powder inhaler (DPI) formulations mostly involves crystallization followed by high energy input size reduction systems (e.g., milling and homogenization), which produces particles with very high surface energy and poor flow property that restricts the efficient dispersion of drug from the formulations. This investigation has used an anti-solvent precipitation crystallization (APC) method of producing inhalable ibuprofen (IBP) crystals for pulmonary delivery from a DPI formulation

Preparation of ibuprofen microparticles by antisolvent precipitation crystallization technique: characterization, formulation, and in vitro performance

This study demonstrates the preparation and characterization of ibuprofen (IBP) microparticles with some excipients by a controlled crystallization technique with improved dissolution performance. Using the optimum concentrations pluronic F127, hydroxypropyl methyl cellulose, D-mannitol, and L-leucine in aqueous ethanol, the IBP microparticles were prepared. The dissolution tests were performed in phosphate buffer saline using a United States Pharmacopoeia dissolution tester at 37°C. The Raman spectroscopy was used to investigate the interactions and distribution of the IBP with the additives in the microcrystals. The prepared IBP microparticles showed higher dissolution compared to that of the smaller sized original IBP particles. The Raman data revealed that the excipients with a large number of hydroxyl groups distributed around the IBP particle in the crystal enhanced the dissolution of the drug by increasing the drug-solvent interaction presumably through hydrogen bonding. The Raman mapping technique gave an insight into the enhanced dissolution behavior of the prepared IBP microparticles, and such information will be useful for developing pharmaceutical formulations of hydrophobic drugs. The controlled crystallization was a useful technique to prepare complex crystals of IBP microparticles along with other additives to achieve the enhanced dissolution profile

Formulation and delivery strategies of ibuprofen: challenges and opportunities

Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID) is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may provide useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms are limited that leads to poor bioavailability at high dose after oral administration. The poor solubility is a problem for developing injectable solution dosage forms. Because of its poor skin permeability, it is difficult to obtain an effective therapeutic concentration from topical preparations. This review aims to give a brief insight into the status of ibuprofen dosage forms and their limitations, particle/crystallization technologies for improving formulation strategies as well as suggesting its incorporation into the pulmonary drug delivery systems for achieving better therapeutic action at low dose

Can Non-Pharmaceutical Interventions Contain the Spreading of Novel Coronavirus SARS-CoV-2 in the Asia Pacific Countries?

A novel coronavirus, namely SARS-CoV-2, has emerged rapidly and overspread worldwide, causing a pandemic disease, COVID-19. Until now, no pharmaceutical interventions specific to the COVID-19 infection has been proven effective. In these circumstances, non-pharmaceutical interventions, for example, banning local and international flights, national lockdowns of cities, social distancing, self-isolation, home-quarantine, the closure of schools and universities, closure of government and private offices, banning of mass gatherings would play a vital role in minimizing the primary reproduction number (R0) in expected level. Many Asia Pacific countries, Bangladesh, China, India, Iran, Nepal, New Zealand, Pakistan, and Vietnam, adopt, practice, and implement those non-pharmaceutical interventions and have success stories. Thereby, non-pharmaceutical interventions can contain the virus's spreading, which further reduces long waiting for the healthcare system's hospitalization and burden

Plausibility of natural immunomodulators in the treatment of COVID-19–A comprehensive analysis and future recommendations

The COVID-19 pandemic has inflicted millions of deaths worldwide. Despite the availability of several vaccines and some special drugs approved for emergency use to prevent or treat this disease still, there is a huge concern regarding their effectiveness, adverse effects, and most importantly, their efficacy against the new variants. A cascade of immune-inflammatory responses is involved with the pathogenesis and severe complications with COVID-19. People with dysfunctional and compromised immune systems display severe complications, including acute respiratory distress syndrome, sepsis, multiple organ failure etc., when they get infected with the SARS-CoV-2 virus. Plant-derived natural immune-suppressant compounds, such as resveratrol, quercetin, curcumin, berberine, luteolin, etc., have been reported to inhibit pro-inflammatory cytokines and chemokines. Therefore, natural products with immunomodulatory and anti-inflammatory potential could be plausible targets to treat this contagious disease. This review aims to delineate the clinical trials status and outcomes of natural compounds with immunomodulatory potential in COVID-19 patients along with the outcomes of their in-vivo studies. In clinical trials several natural immunomodulators resulted in significant improvement of COVID-19 patients by diminishing COVID-19 symptoms such as fever, cough, sore throat, and breathlessness. Most importantly, they reduced the duration of hospitalization and the need for supplemental oxygen therapy, improved clinical outcomes in patients with COVID-19, especially weakness, and eliminated acute lung injury and acute respiratory distress syndrome. This paper also discusses many potent natural immunomodulators yet to undergo clinical trials. In-vivo studies with natural immunomodulators demonstrated reduction of a wide range of proinflammatory cytokines. Natural immunomodulators that were found effective, safe, and well tolerated in small-scale clinical trials are warranted to undergo large-scale trials to be used as drugs to treat COVID-19 infections. Alongside, compounds yet to test clinically must undergo clinical trials to find their effectiveness and safety in the treatment of COVID-19 patients

Solubility of ibuprofen in aqueous ethanol at low ethanol contents

The solubility of ibuprofen was measured in water (W) - ethanol (E) mixtures from 0 to 50% w/w ethanol at 10, 25 and 40 °C by the dissolution method using UV spectrophotometry to determine the ibuprofen concentrations. The UV calibration for ibuprofen in different water - ethanol mixtures showed Beer - Lambert linearity, however the slopes differed, which indicated the structure of the drug is influenced by the solvent system i.e. the water - ethanol ratio. The ibuprofen solubility in water (zero ethanol) is low (~ 50 ppm) but increases near exponentially with increasing ethanol content. At 40 °C, there is phase separation between 34% and 63% w/w E/(E+W). The solubility data will be used to select precipitation crystallizer conditions to directly produce free flowing ibuprofen particles (<5 m) for developing a dry powder inhaler (DPI) formulation for lung delivery

TAILORING OF SOLUBILITY OF IBUPROFEN IN THE PRESENCE OF HYDROPHILIC EXCIPIENTS IN WATER-ETHANOL MIXTURES BY CRYSTALLIZATION METHOD

Objective: The objective of this study was to determine the effect of some commonly used pharmaceutical excipients on the solubility of Ibuprofen (Ibu) in a co-solvent consisting of water (W) and ethanol (E).  Methods: The Ibu solubility studies were carried out by dissolving the drug to equilibrium into aqueous ethanol solvents at a fixed temperature. The temperature of the water bath was kept constant (±0.1 °C of the desired temperatures 10, 25 and 40 °C). The solubility of Ibu was measured by using UV spectrophotometry.  Results: The low solubility (~ 50 ppm) of Ibu without excipients in water (zero ethanol) was observed. However, Ibu solubility was increased near exponentially with excipient containing co-solvent system. The maximum solubility of Ibu (1726 ppm) was occurred in a co-solvent containing 1.52% leucine, 5.22% mannitol, 0.25% HPMC, 1.55% Pl F127 and 10.75% w/w ethanol. The phase separation between 34% and 63% w/w E/(E+W) was observed at 40 °C. The individual effect of Pl F127 on enhancing the Ibu solubility was significant.  Conclusion: The individual addition of leucine, mannitol and HPMC has limited impact on the solubility of Ibu. However, the effect of combining these excipients together on Ibu solubility is significantly high

CRISPR is a useful biological tool for detecting nucleic acid of SARS-CoV-2 in human clinical samples

The recent pandemic of novel coronavirus disease (COVID-19) has spread globally and infected millions of people. The quick and specific detection of the nucleic acid of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) remains a challenge within healthcare providers. Currently, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is the widely used method to detect the SARS-CoV-2 from the human clinical samples. RT-qPCR is expensive equipment and needs skilled personnel as well as lengthy detection time. RT-qPCR limitation needed an alternative healthcare technique to overcome with a fast and cheaper detection method. By applying the principles of CRISPR technology, several promising detection methods giving hope to the healthcare community. CRISPR-based detection methods include SHERLOCK-Covid, STOP-Covid, AIOD-CRISPR, and DETECTR platform. These methods have comparative advantages and drawbacks. Among these methods, AIOD-CRISPR and DETECTR are reasonably better diagnostic methods than the others if we compare the time taken for the test, the cost associated with each test, and their capability of detecting SARS-CoV-2 in the clinical samples. It may expect that the promising CRISPR-based methods would facilitate point-of-care (POC) applications in the CRISPR-built next-generation novel coronavirus diagnostics

Formulation and delivery strategies of ibuprofen: challenges and opportunities

Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID) is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may provide useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms are limited that leads to poor bioavailability at high dose after oral administration. The poor solubility is a problem for developing injectable solution dosage forms. Because of its poor skin permeability, it is difficult to obtain an effective therapeutic concentration from topical preparations. This review aims to give a brief insight into the status of ibuprofen dosage forms and their limitations, particle/crystallization technologies for improving formulation strategies as well as suggesting its incorporation into the pulmonary drug delivery systems for achieving better therapeutic action at low dose