Enhanced bioavailability of metoclopramide HCl by intranasal administration of a mucoadhesive in situ gel with modulated rheological and mucociliary transport properties

Zaki, Noha M.; Awad, Gehanne A.S.; Mortada, Nahed D.; ElHady, Seham S. Abd

doi:10.1016/j.ejps.2007.08.006

Cited by 185 publications

(117 citation statements)

References 78 publications

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“…Existing formulations are often associated with a nasal drip or 'run-off' effect which potentially diminish the bioavailability of nasal formation. A novel development in this area has been the formulation of intelligent response based hydrogel nasal formulations which act to enhance residency within the nasal cavity [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] .…”

Section: Resultsmentioning

confidence: 99%

“…A modified method described by Zaki et al 8 was used to determine the sol-gel transition temperature (Tsol-gel). A sample of each formulation (1 g) was transferred to a glass vial and heated in a dry block (Techne Dri-Block ® DB-2D), initiated at 20 °C and increased by 1 °C after every 5 minutes of equilibration time.…”

Section: Sol-gel Transition (Tsol-gel)mentioning

confidence: 99%

“…Although originally exploited for the delivery of locally acting agents (allergic of infections rhinitis, nasal pluposos and sinusitis) the highly vascularised nature of the nasal cavity has provided a portal for systemic delivery of small molecules and biomolecules 7 . The nasal cavity can provide larger surface area for rapid systemic absorption due to its highly vascularised surface 8 . This non-invasive route not only provides rapid onset of action, but often increased bioavailability in low doses as it bypasses the first pass metabolism 9 .…”

Section: Introductionmentioning

confidence: 99%

“…To achieve this goal, the use of intelligent polymer based systems have now become more commonplace in this field and particularly the use of responsive systems which may respond to the nasal cavity temperature [13][14][15][16][17][18][19][20][21][22] or pH [23][24][25][26][27] have increased amongst researchers. Furthermore, the use of mucoadhesive polymers 4,[27][28][29][30][31][32][33] to enhance the adhesion of the formulations onto the nasal mucosa has further demonstrated the ability to prolong contact time with the mucosa and hence increase bioavailability 10,15,18,23,[34][35][36] .…”

Section: Introductionmentioning

confidence: 99%

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Development and Evaluation of a Novel Intranasal Spray for the Delivery of Amantadine

Lungare

Bowen

Badhan

2016

Journal of Pharmaceutical Sciences

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The aim of this study was to develop and characterise an intranasal delivery system for amantadine (AMT). Optimal formulations (F) consisted of a thermosensitive polymer Pluronic ® 127 (P127) and either carboxy methyl cellulose (CMC) or chitosan (CS) which demonstrated gel-transition at nasal cavity temperatures (34 °C ± 1 °C). Rheologically, the loss tangent (Tan δ) confirmed a three-stage gelation phenomena at 34 °C ± 1 °C and nonNewtonian behaviour. Storage of FCMC and FCS at 4 °C for 8 weeks resulted in repeatable release profiles at 34 °C when sampled, with a Fickian mechanism earlier on but moving towards anomalous transport by week 8. Polymers (P127, CMC and CS) demonstrated no significant cellular toxicity to human nasal epithelial cells up to 4 mg/mL and up to 1 mM for AMT (IC50: 4.5 mM ± 0.05 mM). FCMC and FCS demonstrated slower release across an in-vitro human nasal airway model (43-44 % vs 79 % ± 4.58 % for AMT). Using a human nasal cast model, deposition into the olfactory regions (potential nose-to-brain) was demonstrated upon nozzle insertion (5 mm) whereas tilting of the head forward (15°) resulted in greater deposition in the bulk of the nasal cavity. KEYWORDSParkinson's disease; rheology; nasal; RPMI 2650; nose to brain; thermoresponsive; 3 INTRODUCTION Parkinson's disease (PD) is an ageing associated progressive neurological disorder and affects 1.5 % of the population over 65-years of age 1 , with age-adjusted prevalence rates thought to be around 150 per 100,000 with a suggested mean onset in the 70's 1 . Ageing is the largest single risk factor for the development of PD and the pathogenesis of PD is composed of a range of events leading towards neuronal apoptosis, primarily of degradation of dopamine neurones in the sustantia nigra. The mainstay of clinical drug therapy focuses on increases the levels of dopamine (DA) in the brain, with oral dosing of levodopa being the most commonly used to pharmacological intervention treatment to reverse the symptoms of PD. It is also common to use adjunct therapies in conjunction with levodopa, such as the weak NMDA-type receptor antagonist amantadine, which can aid in blocking dopamine reuptake.

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Section: Resultsmentioning

confidence: 99%

Section: Sol-gel Transition (Tsol-gel)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Development and Evaluation of a Novel Intranasal Spray for the Delivery of Amantadine

Lungare

Bowen

Badhan

2016

Journal of Pharmaceutical Sciences

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“…It has been observed in animal studies that the use of mucoadhesive in situ gel enhances the bioavailability of metoclopramide HCl [9]. Thus, improvement of the delivery system, the technique used in the application as well as drug formulations are necessary to achieve better clinical effects.…”

Section: Drug Distributionmentioning

confidence: 99%