S. A. Hazare*, M. D. Menon, P. S. Soni1, G. Williams2 and G. Brouet2

Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Mumbai - 400 098, India
1Board of Radiation and Isotope Technology and Medical Cyclotron Facility, Mumbai - 400 012, India
2Valois S.A.S (Pharma Division), Route Des Falaises 27100 Le Vaudreuil, France

*Corresponding Author:
S. A. Hazare
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Mumbai - 400 098, India
E-mail: shrutihazare@gmail.com
   
   
  27 October, 2007
Indian J Pharm Sci, 2007, 69 (5): 728-729  

DOI: 10.4103/0250-474X.38496

Abstract

A potential barrier to the widespread use of nasal spray devices for drug delivery has been the variability in dosing because of partial metering, as the patient does not press consistently enough on the actuator of the pump. This could be a serious limitation for the delivery of potent medications. Recently new generation nasal pumps have been developed by Valois which spray only on the full actuation of the pump, and hence ensure accuracy of dosing in intranasal delivery of drugs. The present study aimed to compare the in vivo nasal deposition pattern of two nasal spray pumps- a conventional pump (VP3®) and a new generation pump (EQUADEL®), both developed by Valois S.A.S, France, in human volunteers by SPECT-CT imaging technique.

Materials and Methods

Nasal spray pumps, VP3® and EQUADEL®, were fitted to 5 ml glass containers containing 1 ml of 0.5% methylcellulose in saline and 99mTc DTPA (10-15 mCi). Viscosity was determined by rotational viscometer (Brookfield Viscometer, Model: LVT) and droplet size distribution by laser diffraction apparatus (Mastersizer X, MALVERN), Spray pattern by automatic actuating machine (Machine- NSX from Image Therm Engineering) [1]. For in vivo studies, protocol was approved by Institutional Ethics Committee. Ten healthy male volunteers (20-30 y), screened by ENT surgeon were selected, and informed consent was obtained in writing from each volunteer. Tests were performed on three assembled units each of VP3 and EQUADEL in triplicate. CT scans (GE discovery ST) of all volunteers were recorded. For dosing, volunteers inhaled the spray in a sitting position, and SPECT images were recorded for 10 min, with volunteers in supine position. To calculate deposition area static image was analyzed; SPECT image was superimposed with CT scan, and nasal deposition was quantified in terms of upper to lower (U:L) and inner to outer (I:O) ratios [2] (fig. 1).

Figure

Fig. 1: SPECT-CT images showing nasal cavity divisions

Results and Discussion

Rheograms of 0.25% MC sample (pH 5-6) have shown pseudo-plastic behavior. Droplet size distribution in case of VP3 was slightly larger than EQUADEL (Table 1). Spray pattern analysis showed more variability in case of VP3, although the mean values for both pumps were similar (Table 2). In the in vivo study, the SPECT images were superimposed with CT scans and deposition patterns of the two pumps were compared [3]. The data was analyzed by using Graphpad Prism 4 software. Analysis of the superimposed images revealed that for the I:O and U:L ratios the Equadel pump had less variable deposition when compared to the VP3 pump (Table 3). Some differences between deposition areas (pixel), which corresponds to total dose delivered, are evident; however, these results are not strong enough to differentiate two pumps.

Droplet size distribution D (V, 0.5) pm
  Mean RSD
EQUADEL 49 6%
VP3 60 11%

Table 1: Droplet Size Distribution of Two Pumps

Spray pattern Max. mm. Min. mm
EQUADEL  42 ± 3 35 ± 1
VP3 42 ± 5 35 ± 4

Table 2: Spray Pattern Data of Two Pumps

Volunteer   U:L   I: O Deposition area (pixel)
VP3 Equadel VP3 Equadel VP3 Equadel
1 1.123±0.644 0.920±0.923 0.088±0.086 0.217±0.287 48.33±11.93 49.67±12.10
2 0.191±0.273 0.749±0.557 0.533±0.422 0.285±0.080 45.67±3.06 53.00±1.00
3 0.080±0.130 0.052±0.068 0.311±0.339 0.251±0.133 50.67±8.74 41.67±4.62
4 0.012±0.007 0.030±0.021 0.945±0.943 0.542±0.631 50.00±9.64 55.70±10.02
5 0.924±0.503 0.646±0.339 0.237±0.056 0.479±0.498 63.50±30.41 46.95±23.40
6 0.875±0.491 0.344±0.166 0.385±0.092 0.148±0.097 54.33±13.05 47.67±5.77
7 0.674±0.520 0.492±0.207 0.199±0.016 0.043±0.075 59.00±12.53 42.00±6.24
8 0.214±0.331 0.009±0.016 0.035±0.061 0.085±0.134 40.00±11.14 45.67±20.41
9 0.369±0.220 0.504±0.437 0.613±0.260 0.710±0.539 48.33±7.02 49.67±4.62
10 0.497±0.731 0.567±0.464 0.147±0.228 0.079±0.128 33.33±3.21 41.33±24.38
Mean 0.496±0.387 0.431±0.317 0.349±0.280 0.284±0.224 49.32±8.69 47.33±4.64
Nasal deposition was quantified in terms of radioactivity deposited in inner (I) vs. outer (0), and upper (U) vs. lower (L) regions of the nasal cavity (Data presented are mean±SD, n=3)

Table 3: Regional Deposition Pattern and Deposition Area of Droplets Administered by VP3 and Equadel Pump

In conclusion, in vitro evaluation tests of the two pumps have shown slight differences and the in vivo deposition study showed the Equadel pump to have less variability of deposition. The study reveals the potential of SPECT-CT imaging technique to evaluate spraying devices/formulations for nasal delivery.

Acknowledgements

The authors wish to thank Valois, France for financial assistance, Mr. Rameshwar Prasad, Tata Memorial Hospital for helping in acquiring the data and analysis and Dr. Narayan (ENT surgeon) for initial screening of volunteers.

References