Formulation Development and Evaluation of Freeze-dried Aviptadil Injection using Mannitol as Cryoprotectant (original) (raw)
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Anticipated pharmacological role of Aviptadil on COVID-19
Environmental Science and Pollution Research
Vasoactive intestinal peptide (VIP) is a neuropeptide that is produced by the lymphoid cells and plays a major role in immunological functions for controlling the homeostasis of the immune system. VIP has been identified as a potent anti-inflammatory factor, in boosting both innate and adaptive immunity. Since December 2019, SARS-Cov-2 was found responsible for the disease COVID-19 which has spread worldwide. No specific therapies or 100% effective vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and several drugs have been repurposed, including lopinavir/ ritonavir, remdesivir, favipiravir, and tocilizumab. This paper describes the main pharmacological properties of synthetic VIP drug (Aviptadil) which is now under clinical trials. A patented formulation of vasoactive intestinal polypeptide (VIP), named RLF-100 (Aviptadil), was developed and finally got approved for human trials by FDA in 2001 and in European medicines agency in 2005. It was awarded Orphan Drug Designation in 2001 by the US FDA for the treatment of acute respiratory distress syndrome and for the treatment of pulmonary arterial hypertension in 2005. Investigational new drug (IND) licenses for human trials of Aviptadil was guaranteed by both the US FDA and EMEA. Preliminary clinical trials seem to support Aviptadil's benefit. However, such drugs like Aviptadil in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds.
The objective of this study was to develop an enteric coated tablet of sodium valproate using cellulose acetate phthalate as enteric coating material. Core tablet were prepared by non aqueous granulation method and seal coated with PVP K-30 which act as moisture barrier. This seal coated tablet was further coated with cellulose acetate phthalate to dissolve in the intestinal fluid. The in vitro release result showed that enteric coated were capable of restricting release in the acidic media.The optimized batch is capable of releasing the drug in as same manner of a marketed formulation of sodium valproate.
Drug metabolism and disposition: the biological fate of chemicals, 2018
We report here a novel in vitro enteric experimental system, cryopreserved human intestinal mucosa (CHIM), for the evaluation of enteric drug metabolism, drug-drug interaction, drug toxicity, and pharmacology. CHIM were isolated from the small intestines of four human donors. The small intestines were first dissected into duodenum, jejunum and ileum, followed by collagenase digestion of the intestinal lumens. The isolated mucosa were gently homogenized to yield multiple cellular fragments followed by cryopreservation in a programmable liquid cell freezer and stored in liquid nitrogen. After thawing and recovery, CHIM were found to retain robust P450 and non-P450 drug metabolizing enzyme activities, to demonstrate dose-dependent induction of gene expression of CYP24A1 (approx. 300-fold) and CYP3A4 (approx. 3-fold) by vitamin D3, and induction of CYP3A4 (approx. 3-fold) by rifampin after treatment for 24 hours. Dose-dependent decreases in cell viability quantified by cellular ATP cont...
FEBS Letters, 1991
Biotinylared derivatives of polypeptide hormones have proven to be useful tools for studying the interaction between hormones and their receptors in living cells [f-3) and also For purifying hormone receptofs with avidin affinity columns [4-g]. Esgceially promising are biotinylated derivatives in which the biotin is lirlked to the hormone over a spacer arm. Vasoactivc intestinal polypeptide (VIP) is a 28-amino acid peptide first characterized from porcine duodenum [lo] and has been demonstrated to be involved in numerous biological events (111, The amino acid sequence of pig VIP [ 121 is: His-Ser-Asp-Ala-Val-Pl~e~rhr-Asp-Asn-Tyr-Thr,.,Arg-Leu-Arg-Lys'5-Gln-Met-Ala-Val-Lys2a-Lys2'-Tyr-Leu-Asn-Ser-Ile-Leu-Asn-NH2. VIP has subsequently been isolated from several other species of vertebrates. With the exception of guinea-pig VIP all mammalian forms, including human, have been found to have the same sequence [l 11. Studies of truncated peptides suggest that the biological activity is full) preserved only in the intact peptide [ 131. Calculation by Fournier et al. [14] has suggested that an cr-helix domain spans residues 13-28 segregating the sequence in an amphiphilic manner. By substituting either the hydrophobic or hydrophilic surface it has been suggested that the hydrophilic surface does not participate strongly in receptor binding [ 151. The biotin marker can be readily introduced into VlP via the e-amino BO-B7, were lyophilized and stored at-20°C.
British Journal of Pharmacology, 2005
Vasoactive intestinal peptide (VIP) has been demonstrated in intestinal mucosal neurones and elicits chloride secretion from enterocytes. These findings have led to the proposal that VIP is a secretomotor neurotransmitter. Confirmation of such a role may now be possible with the development of PG 97-269, a high-affinity, selective antagonist of VIP type 1 (VPAC1) receptor, which is expressed by gut epithelial cells. We have evaluated the VIP antagonism and antisecretory potential of this novel compound using in vitro and in vivo models of intestinal secretion. 2 Monolayers of the human colonic cell line (T 84) and muscle-stripped preparations of rat jejunum and human ileum were set up in Ussing chambers for recording of transepithelial resistance and shortcircuit current. Ussing chambers were modified to allow electrical stimulation of mucosal neurones. Effects of PG 97-269 on enterotoxin-induced secretion were investigated in perfused rat jejunum in vivo. 3 PG 97-269 competitively antagonised VIP in T 84 monolayers. In rat jejunum and human ileum, responses to VIP were inhibited as were responses of rat jejunum to electrical stimulation of mucosal neurons. 4 In perfused rat jejunum, PG 97-269 abolished the effects of VIP on fluid and electrolyte transport and attenuated cholera toxin and Escherichia coli heat labile toxin-induced net fluid and electrolyte secretion. 5 PG 97-269 is a competitive antagonist of enterocyte VIP receptors and effectively inhibits responses of rat and human intestinal mucosa to VIP. Antagonism of secretory responses to electrical stimulation of mucosal neurons and lumenal application of enterotoxins imply a secretory role for VIP in these processes.
Formulation and In-Vitro Evaluation of Fenofibrate Dry Emulsion in Hard Vegetarian Capsules
International Research Journal of Pharmacy, 2018
The dry emulsion formulation aims to improve the solubility and dissolution of Fenofibrate. Dry emulsions are an attractive choice because their physical and micro biological stability. They represent a potential oral drug delivery system for lipophilic and low soluble drug substances. Dry emulsions can be prepared by spray drying, lyophilization or rotary evaporation. Dry emulsion prepared here was by lyophilization using flaxseed oil as the lipid phase and HPMC as the carrier. Fenofibrate was the drug of choice as it helps reduce cholesterol and triglycerides (fatty acids) in the blood. Flaxseed oil has been studied for lowering triglycerides. Hence the combination therapy of Fenofibrate and Flaxseed oil in low doses is expected to have a synergistic activity in lowering the cholesterol and triglycerides in the blood. The dry emulsion formed has been incorporated in HPMC (Hydroxyl Propyl Methyl Cellulose) capsules, which provides a vegetarian environment and is a good alternative to gelatin. The formed dry emulsion formulation has been evaluated for the respective parameters in comparison with the marketed variant and the results are obtained.
Vasoactive Intestinal Peptide Is Potentially Lifesaving in Treating COVID-19
SSRN Electronic Journal
Aviptadil, a synthetic form of human Vasoactive Intestinal Peptide (VIP) has been granted FDA Fast Track Designation for the treatment of Critical COVID-19 with respiratory failure and is now in phase 2/3 clinical trials, with initial determinations of safety and non-futility. Rapid recovery from Critical COVID-19 with respiratory failure as been seen in multiple patients treated with open label VIP under FDA Emergency Use IND. VIP binds uniquely to receptors on Alveolar Type II cells in the lung, the same cells that bind the SARS-CoV-2 virus via their ACE2 receptors. VIP protects those cells and the surrounding pulmonary epithelium by blocking cytokines, preventing apoptosis, and upregulating the production of surfactant, the loss of which is increasingly implicated in COVID-19 respiratory failure. Because of its lack of toxicity and low cost of manufacture compared to proprietary biologics, VIP may be uniquely attractive to those focused on global countermeasures against COVID-19.
Background: In North America digestive malfunction in terms of disintegration, dissolution, and absorption of food and nutrients, is a widespread malady. Malabsorption is also an exacerbating factor in most chronic degenerative diseases that might benefit from dietary supplementation. The purpose of this experiment was to determine, as shown by changes in properties of live blood, whether, a novel soy-lecithin-phospholipid-nutrient encapsulation technology could promote rapid bioavailability and bioactivity of a VMP35 nutraceutical formulation encapsulated within its clustoidal multilamellar Soy Lecithin Phospholipid (SLP) liquid SK713 SLP structures. Method: Changes in peripheral blood smears from 38 subjects were measured utilizing peripheral live blood cell imaging (LBCI) with phase contrast microscopy. Results: Compared to baseline and control, consistently and reproducibly, the SK713 SLP technology effected positive changes in the blood as demonstrated by observable morphological, hematological and rheological changes five minutes from intake and sustained for at least 30 minutes post intake. Conclusions: These results showed that the SK713 SLP system makes an important contribution by increasing the potential benefits of dietary supplementation to those patients with compromised digestive processes. We encourage additional research on this novel delivery system believing that it has potential impact on future therapy.