scholarly journals Nasal Delivery of Acute Medications for Migraine: The Upper Versus Lower Nasal Space

2021 ◽  
Vol 10 (11) ◽  
pp. 2468
Author(s):  
Vincent Martin ◽  
John Hoekman ◽  
Sheena K. Aurora ◽  
Stephen B. Shrewsbury
Keyword(s):  
Acute Treatment ◽  
Drug Efficacy ◽  
Hepatic Metabolism ◽  
Rapid Onset ◽  
Systemic Circulation ◽  
Nasal Delivery ◽  
Attractive Alternative ◽  
Gi Tract ◽  
Onset Of Action ◽  
First Pass

The acute treatment of migraine requires effective drugs that are well tolerated and provide rapid and consistent pain relief. Oral tablets are the most commonly used acute treatment for migraine; however, their effectiveness is limited by the rate of gastrointestinal (GI) tract absorption and first-pass hepatic metabolism, and they may not be ideal for patients experiencing GI motility issues. Nasal delivery is an attractive alternative route as it may circumvent GI tract absorption, avoid first-pass metabolism in the liver, and potentially reduce the frequency of GI adverse events. The large surface area and high vascularity within the nose may permit rapid absorption of therapeutics into the systemic circulation, allowing for rapid onset of action. However, the site of drug deposition (upper versus lower nasal cavity) may influence drug pharmacokinetics. Most approved nasal migraine therapies target the lower nasal space where the epithelium is less permeable, and they may be quickly cleared away due to increased ciliary function or dripping from the nose or swallowing, resulting in variable absorption and limited bioavailability. Together with its abundant vascularization, relative mucosal thickness stability, and low clearance rates, the upper nasal space harnesses the benefits of nasal delivery to potentially maximize drug efficacy.

Pharmacokinetic peculiarities of drugs used in the form of rapidly dispersible tablets (oral delivery system)

2020 ◽  
pp. 7-24
Author(s):  
Zhanna Kozlova ◽  
Ivan Krasnyuk ◽  
Yuliya Lebedeva ◽  
Ekaterina Odintsova
Keyword(s):  
Oral Mucosa ◽  
Oral Delivery ◽  
Chemical Properties ◽  
Rapid Onset ◽  
Systemic Circulation ◽  
Systemic Delivery ◽  
Onset Of Action ◽  
Mucosal Drug Delivery ◽  
Physical And Chemical ◽  
Pass Metabolism

Oral mucosal drug delivery is an alternative method of systemic delivery with several advantages over both injectable and enteral methods. Drugs that are absorbed through the oral mucosa directly enter the systemic circulation, passing through the gastrointestinal tract and first-pass metabolism in the liver due to oral mucosa being highly vascularised. This results in rapid onset of action for some drugs because of a more comfortable and convenient way of delivery than the intravenous one. But not all drugs can be administered through the oral mucosa due to characteristics of the oral mucosa and physical and chemical properties of the drug.

Creating systemic oral transmucosal drug delivery strategies: Case study of APL-130277

2012 ◽  
Vol 18 (3) ◽  
Author(s):  
Anthony Giovinazzo ◽  
Nathan Bryson ◽  
Timothy Tankosic
Keyword(s):  
Drug Delivery ◽  
Hepatic Metabolism ◽  
Rapid Onset ◽  
Easy Access ◽  
Patient Acceptance ◽  
Onset Of Action ◽  
Buccal Drug Delivery ◽  
High Level ◽  
Systemic Drug Delivery

This article addresses the strategic application of systemic oral transmucosal* (i.e., sublingual and buccal) drug delivery. Circumvention of first-pass hepatic metabolism in the gut, rapid onset of action, easy access via the oral cavity, easy administration for patients with dysphagia and a high level of patient acceptance are the principal advantages of the oral transmucosal route. Key clinical and commercial strategies driving the development of oral transmucosal formulations are addressed. A case study of Cynapsus Therapeutics' APL-130277, a sublingual apomorphine formulation in clinical development for Parkinson's disease exemplifies the scientific, clinical and commercial considerations for systemic oral transmucosal drug delivery. *Note: In this article, oral transmucosal delivery refers to systemic drug delivery through the sublingual or buccal mucosa. Local delivery to the oral mucosa is not included.

A REVIEW ON BUCCAL MUCOSAL ROUTE OF DRUG ADMINISTRATION

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (08) ◽  
pp. 5-16
Author(s):  
M Bhatt ◽  
◽  
G Bhatt ◽  
P. Kothiyal ◽  
S. Chaudhary
Keyword(s):  
Drug Administration ◽  
Hepatic Metabolism ◽  
Systemic Circulation ◽  
Oral Route ◽  
Moisture Loss ◽  
Direct Access ◽  
Mucosal Route ◽  
First Pass ◽  
Milling Method ◽  
Buccal Films

Oral route is the most preferred rote of drug administration. In oral route buccal mucosal route is one of the advantageous routes of drug administration. This route provides direct access to systemic circulation through the jugular vein, bypassing the first pass hepatic metabolism, which leads to high bioavailability. The drugs having low bioavailability, shorter half life and those who undergoes extensive first pass metabolism are good candidat for this rote. Various formulations have been developed for this routes, one of which is buccal film. Buccal films were prepared by using methods like solvent casting method, hot-melt extrusion method and direct milling method. Buccal films were evaluated for thickness, swelling property, surface pH, drug content, % moisture loss, etc.

scholarly journals Nasal Drug Delivery: A Potential Route for Brain Targetting

2015 ◽  
Vol 1 (2) ◽  
pp. 65 ◽  
Author(s):  
Brahmaiah Bonthagarala ◽  
Shabana P. ◽  
Abbaraju Lakshmi Harini ◽  
Varun Dasari
Keyword(s):  
Drug Delivery ◽  
Nasal Mucosa ◽  
Targeted Drug Delivery ◽  
Drug Transport ◽  
Relative Concentration ◽  
Rapid Onset ◽  
Nasal Drug Delivery ◽  
Onset Of Action ◽  
First Pass ◽  
The Brain

Present review highlights the potential of nasal mucosa as an administration route for targeting the centralnervous system, the brain. Targeted drug delivery seeks to concentrate the medication in the tissues ofinterest while reducing the relative concentration of medication in the remaining tissues. Thus improvingefficacy of the drug and reducing side effects. The nasal mucosa when compared to other mucousmembranes is easily accessible and provides a practical entrance portal for small and large molecules.Intranasal administration offers rapid onset of action, no first-pass effect, no gastrointestinal degradationor lung toxicity and non-invasiveness application and also improves bioavailability. It is thought thatolfactory route of drug transport, by pass the blood-brain barrier and allows the direct transport of drugfrom the nose to the brain. This review provides an overview of strategies to improve the drug delivery tobrain via nasal mucosa and recent advances in this field.

scholarly journals Sublingual spray: a new technology oriented formulation with multiple benefits

2019 ◽  
Vol 10 (4) ◽  
pp. 2875-2885 ◽  
Author(s):  
Aravindhanthan V ◽  
Anjali P B ◽  
Arun Radhakrishnan
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
New Technology ◽  
Rapid Onset ◽  
Regulatory Agencies ◽  
Onset Of Action ◽  
First Pass ◽  
Delivery Technology ◽  
Pass Metabolism

Sublingual drug delivery system was a well-established platform for delivering the drug that need to exhibit quick action without any first-pass metabolic effect, but various pitfall in the regular sublingual drug delivery systems such as a tablet, capsule etc., that can be overcome by novel sublingual drug delivery technology such as particulate sublingual spray. Sublingual spray for drug administration has gained attention in the market since it proved its propensity to by-pass the first-pass metabolism and to initiate a rapid onset of action due to its atomized micro particulate nature, which is significantly higher than the other sublingual formulations. The approval of sublingual spray by the regulatory agencies may commence further research in this field by subsuming various essential drugs for indications such as cancer pain, cardiovascular issue etc. This article comprises a detailed study on the drawback of conventional sublingual drug delivery system and the approach by which these drawbacks can be overruled by spray technology in the sublingual area and the, in-depth mechanism of drug delivery through sublingual with the help of atomization followed by the entire formulation strategy along with evaluation and industrial perspective of the sublingual spray dosage form as a future tool of patient-friendly drug delivery.

scholarly journals Topical levocabastine—a review of therapeutic efficacy compared with topical sodium cromoglycate and oral terfenadine on days with high pollen counts

1995 ◽  
Vol 4 (7) ◽  
pp. S21-S25 ◽  
Author(s):  
Marianela de Azevedo
Keyword(s):  
Sodium Cromoglycate ◽  
Rapid Onset ◽  
Attractive Alternative ◽  
Eye Drops ◽  
Therapeutic Approaches ◽  
Onset Of Action ◽  
High Pollen ◽  
Pollen Counts ◽  
First Line Therapy ◽  
Comparative Trials

Levocabastine is a new H1-receptor antagonist specifically developed for the topical treatment of seasonal allergic rhinoconjunctivitis. Clinical experience to date clearly demonstrates that levocabastine eye drops and nasal spray are effective and well tolerated for the treatment of this allergic disorder. Analysis of data from a number of comparative trials reveals that topical levocabastine is at least as effective as sodium cromoglycate and the oral antihistamine terfenadine, even on days with high pollen counts (≥ 50 pollen particles/m3) when symptoms are severe. Coupled with a rapid onset of action and twice daily dosing, these findings make topical levocabastine an attractive alternative to other therapeutic approaches as a first-line therapy for the treatment, of this common condition.

Efficacy and Safety of Rizatriptan Wafer for the Acute Treatment of Migraine

Cephalalgia ◽  
1999 ◽  
Vol 19 (5) ◽  
pp. 525-532 ◽  
Author(s):  
SP Ahrens ◽  
MV Farmer ◽  
DL Williams ◽  
E Willoughby ◽  
K Jiang ◽  
...  
Keyword(s):  
Pain Relief ◽  
Acute Treatment ◽  
Rapid Onset ◽  
Onset Of Action ◽  
Double Blind ◽  
Experienced Pain ◽  
Freeze Dried ◽  
New Formulation ◽  
Outpatient Study ◽  
Dosage Formulation

Rizatriptan is a potent, highly selective 5HT1B/1D agonist with rapid onset of action for acute treatment of migraine. Rizatriptan wafer1 is a novel, freeze-dried dosage formulation of rizatriptan which rapidly disintegrates on the tongue, is swallowed with saliva, and may be taken without liquids. The efficacy and tolerability of rizatriptan wafer were examined in a placebo-controlled, double-blind, outpatient study in 555 migraineurs. The primary efficacy endpoint was pain relief at 2 h. From 30 min onwards, significantly more patients experienced pain relief and became pain-free after rizatriptan 10-mg wafer compared to placebo. At 2 h, the percentage of patients with pain relief was significantly higher after rizatriptan 10-mg wafer (74%), 5-mg wafer (59%) compared with placebo (28%). Rizatriptan 10-mg wafer was superior to rizatriptan 5-mg wafer on pain relief at 1.5 and 2 h ( p<0.05). Significantly more patients were pain-free at 2 h after rizatriptan 10-mg wafer (42%), 5-mg wafer (35%) compared with placebo (10%). Both doses of rizatriptan wafer were well tolerated. Rizatriptan wafer is a convenient, highly effective new formulation for acute treatment of migraine.

scholarly journals Overview of Newer Glucocorticosteroid Preparations for Inflammatory Bowel Disease

1990 ◽  
Vol 4 (7) ◽  
pp. 407-414 ◽  
Author(s):  
R Brattsand
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Topical Therapy ◽  
Hepatic Metabolism ◽  
Systemic Circulation ◽  
First Pass Metabolism ◽  
First Pass ◽  
Inflammatory Bowel ◽  
Bowel Mucosa ◽  
Pass Metabolism

Because the glucocorticosteroid receptor seems to be uniform in the human body, there is currently no support for a possibility of separating the therapeutic and adverse glucocorticosteroid actions at the receptor level. However, based on a new generation of glucocorticosteroids characterized by a high first pass metabolism in the liver, it seems possible today co reach a more selective topical therapy of inflammatory bowel disease. The properties of three new glucocorticosteroids are presented: the highly potent budesonide, fluticasone propionate and tixocortol pivalate - the latter with only low topical potency. Their properties can be exemplified by budesonide, which is currently the best documented compound. The topical potency of budesonide is 200 and 15 times higher than chose of hydrocortisone and prednisolone, respectively. This means that there is a high potential for anti-inflammatory and immunosuppressive actions on rectal and bowel mucosa. The compound is metabolically stable in the bowel compartment, which allows full retention of glucocorticosteroid activity in the target organ. However, when absorbed and distributed to the liver, there is a 90% first pass hepatic metabolism co metabolites of very low potency. This suggests that after topical application to rectal or bowel mucosa, glucocorticosteroid activity in the systemic circulation is low. This is in contrast to prednisolone, which has a hepatic first pass metabolism of just 20%.

scholarly journals SUBLINGUAL DRUG DELIVERY: AN INDICATION OF POTENTIAL ALTERNATIVE ROUTE

2017 ◽  
Vol 9 (6) ◽  
pp. 5 ◽  
Author(s):  
Puja Saha ◽  
Sushma Verma ◽  
Pratik Swarup Das
Keyword(s):  
Blood Vessels ◽  
Psychiatric Patients ◽  
Life Cycle Management ◽  
Ventral Surface ◽  
Rapid Onset ◽  
Systemic Circulation ◽  
Onset Of Action ◽  
The People ◽  
Short Period ◽  
Suitable Form

Sublingual literally meaning is “under the tongue”, refers to a method of administrating substance via mouth in such a way that the substance is rapidly absorbed via blood vessels under tongue. Sublingual route is a useful when rapid onset of action is desired with better patient compliance than orally ingested tablets. Drugs that are given sublingually reach directly in to the systemic circulation through the ventral surface of the tongue and floor of the mouth. The portion of drug absorbed through the sublingual blood vessels bypasses the hepatic first‐pass metabolic processes giving acceptable bioavailability. As nowadays most of the people need effective relief within a short period of time so sublingual is the most suitable form of administration. New sublingual technologies address many pharmaceutical and patient needs, ranging from enhanced life‐cycle management to convenient dosing for paediatric, geriatric, and psychiatric patients with dysphagia.

EFFECTS OF ORAL ASPIRIN ON PLATELET AND VASCULAR CYCLOOXYGENASE ACTIVITY IN RATS WITH PORTACAVAL SHUNT

1987 ◽  
Author(s):  
C Cerletti ◽  
M C Gombino ◽  
S Possaghe ◽  
F Bucchi ◽  
Z M Chen ◽  
...  
Keyword(s):  
Inferior Vena ◽  
Vena Cava ◽  
Portacaval Shunt ◽  
Hepatic Metabolism ◽  
Systemic Circulation ◽  
Cyclooxygenase Activity ◽  
First Pass ◽  
Anaesthetized Rats ◽  
Oral Aspirin

Oral aspirin can be extensively hydrolysed to salicylate in stomach and liver before entering the systemic circulation. “Pre-systemic” acetylation of the platelets may thus occur during aspirin absorption. This may result in concomitant sparing of peripheral vascular cyclooxygenase mainly exposed to salicylate. We tested whether the “biochemical selectivity” of oral aspirin as an inhibitor of platelet vs. vascular cyclooxygenase would be reduced by elimination of the “first-pass” hepatic metabolism. A portacaval shunt was inserted in anaesthetized rats by connecting the portal vein to the inferior vena cava through a “Y” heparinized polyethylene PE 60-160 cannula. Sham operated rats acted as controls. 90 min after recovery from anaesthesia rats were given aspirin orally (10 mg/kg) and 45 min later serum TxB2 and 6-keto-PGF la formation by vascular rings were evaluated by radioimmunoassay. Serum TxB2 was completely suppressed in all animals; in contrast, vascular 6-keto-PGF la was significantly reduced (by 40-60* in aorta and vena cava) in rats with portacaval shunt but not in controls. The results in rats with portacaval shunt were similar to those previously obtained after i.v. aspirin. 15 min after aspirin administration, plasma levels of unmetabolized drug measured by HPLC were significantly higher in rats with portacaval shunt (0.56±0.16 μg/ml; n= 5) than in sham operated controls (0.16±0.22 }μg/ml; n= 5). This study directly supports the role of “ first-pass” hepatic metabolism in determining the “biochemical selectivity” of oral aspirin.

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