Coronavirus disease-2019 (COVID-19) is caused by coronavirus-2 (SARS-CoV-2) and has produced a global pandemic. As of 22 June 2021, 178 million people have been affected worldwide, and 3.87 million people have died from COVID-19. According to the Centers for Disease Control and Prevention (CDC) of the United States, COVID-19 virus is primarily transmitted between people through respiratory droplets and contact routes. Since the location of initial infection and disease progression is primarily through the lungs, the inhalation delivery of drugs directly to the lungs may be the most appropriate route of administration for treating COVID-19. This review article aims to present possible inhalation therapeutics and vaccines for the treatment of COVID-19 symptoms. This review covers the comparison between SARS-CoV-2 and other coronaviruses such as SARS-CoV/MERS, inhalation therapeutics for the treatment of COVID-19 symptoms, and vaccines for preventing infection, as well as the current clinical status of inhaled therapeutics and vaccines.
The aim of the present study was to improve the dissolution, permeability and therefore oral bioavailability of the fexofenadine hydrochloride (FEX), by preparing lipid surfactant based dispersions using self-emulsifying carriers, i.e. Gelucire 44/14 (GLC) and d-α-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS or TPGS). The reprecipitation studies were conducted using these carriers to evaluate inhibition of reprecipitation by maintaining super saturation state. The aqueous solubility of the FEX was increased linearly with increasing GLC, TPGS concentrations as verified by the phase solubility studies. The dispersions of FEX were prepared in different drug/GLC (GD) and drug/TPGS (TD) ratios by melt method and evaluated. The prepared dispersions showed improved dissolution rate in distilled water as dissolution media and highest dissolution rate was achieved with dispersions prepared using TPGS. The solid state characterization was carried by differential scanning calorimetry and scanning electron microscopy indicated reduced crystallinity of the drug. Fourier transform infrared spectroscopy revealed the compatibility of drug with carriers. The ex vivo permeation studies conducted using intestinal gut sac technique, resulted in reduced efflux of the drug by inhibiting intestinal P-glycoprotein from the dispersions. The in situ perfusion studies and in vivo pharmacokinetic studies in male wistar rats showed improved absorption and oral bioavailability from the prepared dispersions as compared to pure drug.
The objective of this study was to enhance dissolution and permeation of a low soluble, absorbable fexofenadine hydrochloride (FFH) by preparing solid dispersions using polyethylene glycol 20,000 (PEG 20,000) and poloxamer 188 as carriers. The phase solubility measurement for the supplied FFH revealed a linear increase in the solubility of fexofenadine with increasing carrier concentration in water (1.45 mg/mL to 11.78 mg/mL with 0% w/v to 30% w/v PEG 20,000; 1.45 mg/mL to 12.27 mg/mL with 0% w/v to 30% w/v poloxamer 188). To select the appropriate drug carrier concentration, a series of solid dispersions were prepared in the drug carrier weight ratios of 1:1, 1:2 and 1:4 by fusion method. The solid dispersions composed of drug carrier at 1:4 weight ratio showed highest dissolution with the time required for the release of 50% of the drug <15 min compared to the supplied FFH (>120 min). The intestinal absorption study presented a significant improvement in the absorption of drug from the solid dispersions composed of poloxamer 188 than PEG 20,000. In summary, the solid dispersions of FFH prepared using PEG 20,000 and poloxamer 188 demonstrated improved dissolution and absorption than supplied FFH and could be used to improve the oral bioavailability of fexofenadine.
Central nervous system (CNS) disorders, such as psychiatric disorders, neurodegeneration, chronic pain, stroke, brain tumor, spinal cord injury, and many other CNS diseases, would hugely benefit from specific and potent peptide pharmaceuticals and their low inherent toxicity. The delivery of peptides to the brain is challenging due to their low metabolic stability, which decreases their duration of action, poor penetration of the blood-brain barrier (BBB), and their incompatibility with oral administration, typically resulting in the need for parenteral administration. These challenges limit peptides’ clinical application and explain the interest in alternative routes of peptide administration, particularly nose-to-brain (N-to-B) delivery, which allows protein and peptide drugs to reach the brain noninvasively. N-to-B delivery can be a convenient method for rapidly targeting the CNS, bypassing the BBB, and minimizing systemic exposure; the olfactory and trigeminal nerves provide a unique pathway to the brain and the external environment. This review highlights the intranasal delivery of drugs, focusing on peptide delivery, illustrating various clinical applications, nasal delivery devices, and the scope and limitations of this approach.
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