Evaluation of pellets prepared using factorial experimental designs.

05/21/2009

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By Dr. Shruti Bhat

 The pellets were evaluated and characterized for various physical measurements:

1.    Particle size analysis: Studied using Sieve analysis and microscopy.

2.    Yield: the percentage of desired fraction 22/30 mesh fraction of pellets was calculated.

3.    Bulk density: the bulk density was measured at 650 strokes / 15 mins.

4.    True density: the true density of pellets was determined by volume –displacement method in a pycnometer using n-hexane.

5.    Porosity: porosity was calculated as = bulk volume – True volume /  Bulk volume 

6.    % Index hardness –friability (%IHF): pellet hardness was calculated on the basis of the results of the friability test. For this purpose 00 g of pellets (2/30 mesh fraction) were placed in a friabilator and rotated for 10 mins at 250 revolutions. The pellets were then screened to remove the fines. The % index of hardness was calculated as: 

% Index of hardness- friability: residue (g) x 100 / Weight of the sample

7.    Angle of repose (Φ): The angle of repose was determined by the “fixed height method” ad was calculated using the following formulation:

         Tan (Φ) = pile height / pile radius

The results are recorded and Yates method was employed to calculate the significance of parameters and their interaction. 

RESULTS AND DISCUSSION of this article has been omitted to maintain confidentiality of experimental work. Interested readers are requested to contact me at 1-514-743-6159 or email drshrutibhat@email.com 

CONCLUSION:

  1. It is possible to prepare beads with desirable sphericity by controlling the critical parameters. Concentration of sugar (binder) drying between 2 spray operations and pan speed are the critical factors determining the pellet properties.
  2. The results obtained enabled optimum range for process variables to be defined.
  3. A factorial design allowed the evaluation of main effects and interactions.
  4. Definition of objectives and preliminaries calculation showed predictable results for the pan.
  5. Interpretation of results permitted the definition of the limits of the experimental parameters and specifications of values.
  6. Solving problems with this technique is of real interest for qualification and quantification of parameters wrt effects and interaction.
  7. Conventional coating pan is more adaptable for use in pelletization as compared to the dish pelletizer. The beads obtained using pan are with a narrow size distribution, low friability index and high flow ability.
REFERENCES:

1.      O’Connor R.E., Holliney J., Schwartz J.B. “Processing and evaluation of spheres prepared from commercially available excipients : spheronization – I’, Amer.J.Pharm, 156 : 80 (1984).Gajados B,” Rotary granulators: evaluation of process technology for pellet production using a factorial experimental design “ Drugs mad in Germany, 27: 30 (1984).

2.    Woodruff C.W., Nuessle N.O., “ Effect of processing variable in particles obtained by extrusion- spheronization processing “ J.Pharm. Sci, 61: 787 (1972).

3.    Fonner D.E., Banker G.S., Schwarbrick J.” Micromeritics of granular pharmaceutical solid (I)”. J.Pharm. Sci., 55 :181 (1986)
 

 

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Factorial designs in pelletization and bead technology-

05/19/2009

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by Dr. Shruti Bhat


INTRODUCTION:

Particle coating has gained more importance with the advent of sustained and controlled release capsule dosage forms (Ref 1-5).

Pellet shows certain merits:

  1. They maximize drug absorption.
  2. High load concentration of bioactive agents may be avoided
  3. Minimize the risk of unwanted release of active constituents and avoid dose dumping.
  4. Show longer and more predicted transition time in git and also les immobilization near restriction in git.
Non-pareil seeds of sugar and other materials have been in use for the last 50 years in sustained and controlled release dosage forms. Excepting homeopathic sugar beads, non-pareil seeds are not available in India. It was therefore considered of interest to optimize the conditions for preparing non-pareil seeds and is being reported here.


REFERENCES:

  1. Conine J.W. ,Hadley H.R., “ Preparation of mall solid pharmaceutical spheres”, Drugs and Cosmetics Ind., 90: 38 (1970).
  2. Blythe R.H., U.S. Patent 2,783,303 (1956). 
  3. Fisher C.E., Wilson C.H. “spherical beads “ US Patents 3,092,553 (1963). 
  4. Gamlen M.J.”Pellet manufacture for controlled release”. Manuf. Chem. 56:55 (1985).
  5. Wan L.S.C., Jeyerbaran T, “Operating conditions for the formulation of pellets”, Chem, Pharm. Bull, 31: 5449 (1985).
 Construction of experimental design:

Various parameters viz. Binder concentration, drying interval, pan/dish speed were selected. The aim of the study was evaluation of variables of experimental response passing from one limit to the other by employing the 23 factorial design. The pellets so formed were evaluated for size and size distribution, density, hardness –friability, angle of repose, yield etc.

Construction of the design involved the selection of the parameters and the choice of desired effects. The parameters were divided into:

  1. Critical parameters and levels
  2. Non-critical parameters and levels 

 

Critical parameters included- 

X 1: Binder concentration :(+): NMT 500ml of A;  (-): NMT 300 ml of B

X2: Drying interval between 2 spray operations: - (+): 10 mins;   (-): 20 mins.

X3: Coating pan/dish speed: - (+): 32 rpm;  (-):  25 rpm

Non-critical parameters included-


X4: no of spray operations NMT 25.

X5: Spray rate of binder solution 2.5 ml/min.

X6: Pressure of spray solution 1.5-2.0 kg/cm2.

X7: Dusting powder added.

X8: Optimum particle size of DCP, 0.225 mm.

X9 : Angle of inclination of coating pan 60 o and dish pelletizer 45 o

X10: Drying time post pelletization 5 hours at 40 deg. C.

X11: Size and shape of the nozzle L fluid nozzle with 1 mm bore.

Formation of pellets:

The material 200 g of DCP engranules was charged into the pan/dish, which was allowed to rotate at the set angle and speed. The binder solution was sprayed on the feed to form pellets. The experiments followed 23 factorial series. The pellets formed were dried in an oven at 40 deg.C for 5 hours.

 Another optimization design which could be used greatly in pharmaceutical research is Plackette-

For inquiries please contact 1-514-743-6159 or email drshrutibhat@gmail.com

 

 

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