Optimization and evaluation of bilayer tablet of probenecid

The main objective of my research work is to develop a bilayer tablet of Probenecid, in which one layer is immediate layer for immediate action and second layer is the sustain release layer for maintaining the dose of the drug. Probenecid is frequently administered up to 3 times in a day. So, the reducing dosing frequency by sustained release tablet.


Introduction
Oral route has been the most widely used and most convenient route for the drug delivery.Oral route of administration has received more attention in the pharmaceutical industry and research field because of the flexibility in designing of dosage form and constraints like sterility and potential damage at the site of administration.
Approximately 50% of the drug delivery system available in the market is oral drug delivery system which has more advantages due to patient acceptance and easy to administration.The oral absorption of drug is often limited due to short GRT i.e. the time required for the content of the stomach to enter into small intestine.
Drugs that are easily absorbed from the GIT and have a short half-life are eliminated quickly from the blood circulation so they require frequent dosing.To avoid this drawback, the oral sustain/controlled release formulation have been developed in an attempt to release the drug slowly in to the GIT and maintain the effective drug concentration in the serum for longer period of time.
All the pharmaceutical formulation for systemic effect via oral route of administration must be developed within intrinsic characteristics of gastrointestinal physiology.The needs of GIT physiology, Pharmacodynamics, pharmacokinetics & formulation design is essential to achieve a systemic approach to the successful development of an oral formulation dosage form.The scientific framework required for the successful development of an oral drug delivery system consists of basic understanding of the following three aspects:  Physicochemical, pharmacokinetic & pharmacodynamic characteristics of the drug. The Anatomical and physiological characteristics of GIT. Physicochemical characteristics & drug delivery system and type of dosage form design.
The manufacture of multilayer tablets has been successful for over 50 years and one of the early scientific evaluations of layered tablets was published by Stephenson (1961).New machine designs developed during the late 60s have made it possible to check the weight of individual layers by sampling without stopping the machine, providing in-process control facilities to ensure correct dosing, however, despite this, a considerable amount of expertise is still required to formulate these tablets and to ensure consistent manufacture to satisfy regulatory requirements.One problem that causes great concern is the delamination of layered tablets which has become a more obvious problem with the increase in compression speed on modern high-speed rotary machines.Magnesium stearate 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 Talc 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 Total weight

Conclusion
In the present study Probenecid 250 mg tablets have been formulated and developed using direct compression and dry granulation technique, to provide a safe, highly effective method for treating rheumatoid arthritis, pain and inflammation.While reducing undesirable adverse effects.Pre and post formulation parameters were studied for the formulated batches.The result of all the physical and in-vitro dissolution data concluded that bilayer tablet (S3, I3) was the most promising formulation.The trial conducted with the consecutive three batches revealed relative standard deviation below 2 %, indicative the insignificant batch-to-batch variation that can be overcome if processes are run out in a controlled manner.

Figure 1 Figure 2
Figure 1 IR spectra of Drug

Figure 3
Figure 3 UV spectra of the sample drug

Table 1
List of Materials

Table 2
List of Equipment

Table 3
Physical properties of Probenecid

Table 9
Infrared characteristics of Probenecid drug sample S. No. Wave no.(cm-1) Interpretations

Table 10
Composition of Probenecid tablet layers (Immediate)

Table 12
Hardness test for immediate release layer

Table : 13
Hardness test for sustained release layer Where all values are mean ±S.D. for n=3

Table 14
Percent drug content of immediate release layer

Table 15
Percent drug content of sustained release layer Where all values are mean ±S.D. for n=3

Table 16
In-vitro dissolution studies of immediate release layers of Probenecid

Table 17
In-vitro dissolution studies of sustained release layers of Probenecid

S.No. Time (hrs) S1 S2
Where all values are mean ± S.D. for n=3