PERFORMANCE OF SUGAR SPHERES IN NITROGLYCERIN SR FORMULATION

ABSTRACT: Core spheresTM-NCS are a widely used core substance for sustained-release pellet formulations.  This paper reviews the formulation and evaluation development of Nitroglycerin SR pellets by layering process on Core spheres TM-NCS.

Finally, the article focuses on the processing time and the properties obtained in drug-loading process  which could be are better then using traditional extrusion process.

INTRODUCTION: There are numerous procedures for pelletization, with two fundamentally competing concepts.2 On the one hand, the use of Core spheresTM-NCS, which are then coated with the active substance, and on the other, direct pelletization of active substance/excipient mixtures.1

In the first option, Sugar Core spheresTM-NCS (also called neutral pellets, nonpareil seeds, microgranules or sugar beads) are produced, preferably using a layered sugar-coating structure. The result is sugar spheres with sufficient mechanical stability for further processing. The ideally rounded sugar spheres classed in closely graduated particle sizes are then coated with the active substance and sustained release additives. The core of the finished pellet contains no active substance itself so that this solution is used for low-dose substances or substances with a high effect/dose relation.3 But the use of small sugar spheres and corresponding procedures also makes it possible to use this method to produce pellets containing more than 75% active substance.

In the second concept, pelletization already includes the active substance itself. The procedures developed here consist of fluid bed multiprocessor (UMANG FLUID BED MULTIPROCESSOR UFBM 120LTS), or extrusion(TWIN SCREW EXTRUDER UTCE 70) followed by spheronization (SPHERONIZER USPH 700), whereby the initially cylindrical particles are then rounded out in a second step.5,6 

STUDY DESIGN: First, the  Sugar Core spheresTM-NCS was analysed for their sphericity before and after dry processing in a fluid bed multiprocessor (UMANG FLUID BED MULTIPROCESSOR UFBM 120LTS) and were examined under electronic microscope.

Next, the spheres were drug-layered and covered with Sustained Release coating.

The resulting spheres were tested for their API load and bulk density in order to analysed the accomodated amount required for capsules or tablets.

Finally, the loaded spheres were tested for the In-vitro release pattern according to USP pharmacopoeia.

MATERIALS & METHODS

Equipment List:

Vibro Sifter:Premek

Stirrer: REMI

Tray Dryer: Umang Pharmatech

Fluid Bed Multiprocessor: UmangPharmatech

Electronic Microscope: Labomed( X Rii)

Dissolution Tester: Lab India

Ingredient List:

Diluted Nitroglycerin

Sugar Core spheresTM-NCS

P.V.P.K 30

Isopropyl Alcohol

Shellac

Talcum

Ethyl Cellulose

Diethyl Phthalate

Preparation of Nitroglycerin SR Pellets

Nitroglycerin SR Pellets could be produced by drug loading method by using fluid bed multiprocessor (UMANG FLUID BED MULTIPROCESSOR UFBM 120LTS)  as well as traditional method of extrusion (TWIN SCREW EXTRUDER UTCE 70) and spheronization (SPHERONIZER USPH 700). In order  to obtain comparable results, all the process parameters as well as qualitative and quantitative  formulations were kept similar for  both the process.

The drug loading process using Sugar Core spheresTM-NCS as a core material took less time as compare to extrusion and spheronization process.

RESULTS AND DISCUSSIONS

Particle size distribution

The particle size were almost similar in both the process as shown in Figures given below  but the particle size distribution were better and regular spherical shaped prepared by drug loading method.

Figure1: Particle Size Distribution obtained from Extrusion process.

Figure 2: Particle Size Distribution obtained from Drug Loading process.

Dissolution Studies

Dissolution testing of the Nitroglycerin SR Pellets produced with Sugar Core spheres TM-NCS showed results complies with US Pharmacopoeia as shown in the below table.

1hr - NMT35%

4hr - NMT 50%

8hr - NLT 75%

Table 1: Dissolution Release profile of  Nitroglycerin SR Pellets.

Below Figure 3 shows the comparative dissolution profile of Nitroglycerin SR Pellets coated on Sugar Core spheresTM-NCS by drug loading method(F1) and Nitroglycerin SR Pellets manufactured from traditional methods (F2).

Figure 3: ComparativeDissolution profile for

F1- Drug Loading Process

F2- Extrusion process

SUMMARY & CONCLUSION

The preformulation studies shows satisfactory results for both manufacturing process but the use of Core spheresTM-NCS in drug loading method using fluid bed multiprocessor (UMANG FLUID BED MULTIPROCESSOR UFBM 120LTS)  shows the better particle size distribution range as compare to pellets obtained from traditional method.

The dissolution test results also showed the higher and within the pharmacopoeial range of drug release patter for Core spheresTM-NCS in drug loading method while the traditional method of extrusion and spheronization showed low drug release profile.

REFERENCE

1.      D. Werner, Pharma International, 2, 70–77 (1984).

2.      I.Ghebre-Sellassie,Pharmaceutical Pelletization Technology (Marcel Dekker Inc., New York, NY, USA,989)

3.      K.H Bauer et al., Überzogene Arzneiformen(Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, Germany, 1988) pp 40-49.

4.      United States Pharmacopoeial Convention, National Formulary, 23rd edition, Rockville, MD, USA (2005).

5.      E. Nürnberg and J. Wunderlich, Pharm. Technol. Int. 11(2), 41-47 (1999) and Pharm. Technol. Int. 11(3), 30-34 (1999).

6.      M. Niskanen et al., Pharm. Technol. Int. 2(1O), 22-28 (1990) and Pharm. Technol. Int. 2(11), 32-36 (1990).