Formulation and in vitro Evaluation of Floating Capsules of Theophylline

Sustained release floating capsules for theophylline were fabricated using drug:polymer ratio of 30:70. The hydrocolloids were used in different proportions and four formulations were prepared. These formulations were optimized on the basis of buoyancy, matrix integrity, duration of floating and in vitro drug release. All the four formulations showed good buoyancy and matrix integrity. The duration of floating was more than 12 h for all formulations. In vitro drug release study of these formulations indicated controlled release of theophylline and about 76 percent drug was released at the end of 12 h.

monostearate and magnesium stearate.They were of analytical grade and were used as procured.
Before actual formulation, an initial study was carried out to find out the optimum combination of drug and polymers.For floating capsules, hydrocolloids of natural as well as semi synthetic origin were selected.The hydrocolloids selected were hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose and sodium carboxymethylcellulose.In addition to these hydrocolloids, tragacanth was also used.The drug and polymers were taken in a ratio ranging from 90:10 to 10:90.This was done to select the optimum combination of drug polymer ratio in the ß oating drug delivery device in such a way that it would pass the tests of buoyancy, matrix integrity and duration of floating in 0.1 N HCl.The other excipients used were calcium phosphate dibasic, ethyl cellulose, mannitol, and glycerol monostearate and magnesium stearate.The hydrocolloids alongwith the excipients were blended homogenously with the drug.The blended mixture was then Þ lled in the colorless transparent gelatin capsules.
The Þ lled capsules were then observed for buoyancy, matrix integrity and duration of floating (Table 1).From the Table, it was clear that formulation G containing drug and polymers in the ratio of 30:70 remained buoyant in 0.1 N HCl for more than 12 h and maintained the shape.So this combination was selected for further study to incorporate the Sustained release fl oating capsules for theophylline were fabricated using drug:polymer ratio of 30:70.The hydrocolloids were used in different proportions and four formulations were prepared.These formulations were optimized on the basis of buoyancy, matrix integrity, duration of fl oating and in vitro drug release.All the four formulations showed good buoyancy and matrix integrity.The duration of fl oating was more than 12 h for all formulations.In vitro drug release study of these formulations indicated controlled release of theophylline and about 76 percent drug was released at the end of 12 h.Key words: Theophylline, fl oating drug delivery system, sustained release Floating drug delivery system is an oral dosage form designed to prolong the residence time of dosage form within the GI tract 1 .Such dosage form having density less than that of the gastric ß uid ß oats on the gastric juice for an extended period of time while slowly releasing the drug.On contact with the gastric ß uid, the intragastric ß oating capsule forms a water impermeable colloid gel barrier around its surface and maintains a bulk density of less than 1.So, it remains buoyant in the gastric ß uid in stomach until the entire loading dose has been released.This drug delivery system not only prolongs GI residence time but does so in an area of the GI tract that could maximize drug reaching its absorption site in solution and hence ready for absorption.In the present study, hydrodynamically balanced system approach has been selected to control the delivery of theophylline for longer period in stomach from ß oating drug delivery system.
Theophylline, one of the most popular drugs, is used to treat bronchial asthma.Peak serum theophylline concentration occurs 1-2 h after ingestion of liquid preparations, capsules and uncoated tablets and between 4 and 12 h after ingestion of sustained release preparations.Optimum serum theophylline concentration ranges from 10-20 μg /ml 2-6 .It has an average half-life of 8.7 h but in case of smokers, it is 4.4 h.Hence, it requires frequent dosing for achieving therapeutic drug concentration in the target tissue.The objective of present study was to formulate ß oating capsules of theophylline to deliver the drug continuously with set limits of dissolution proÞ le and minimum ß oating time of 8 h.
Theophylline was obtained from Nucron Pharmaceuticals Ltd, Pune.Hydroxypropylmethylcellulose (HPMC K4M) and hydroxyethylcellulose (HEC) was obtained from Amrut Pharmaceuticals, Thane.Ethylcellulose (EC), methylcellulose (MC K4 M) and sodium carboxymethylcellulose (Na-CMC) was obtained from Loba Chemie, Mumbai.The other excipients used were calcium phosphate dibasic, mannitol, and glycerol -denotes non-buoyant/non-intact capsule and + indicates buoyant/intact capsule 0.1 N HCl and temperature was maintained at 37±0.5 0 throughout the study.The duration of ß oating is the time the capsule ß oats in the dissolution medium.
In vitro drug release was studied using USP 24 paddle dissolution apparatus II 7 in 900 ml of 0.1 N HCl at 37±0.5 0 and at 100 rpm.An aliquot of 2 ml of the sample was withdrawn at regular intervals and the same volume of prewarmed (37±0.5 0 ) fresh dissolution medium (0.1 N HCl) was replaced.The samples withdrawn were Þ ltered and drug content in each sample was analyzed after suitable dilution by GBC-UV/Vis 911A Spectrophotometer at 270 nm.
The actual drug content in the formulations was then calculated from the standard curve prepared with theophylline in 0.1 N HCl.
Capsules of all the formulations were found to pass the tests for physical parameters like buoyancy, matrix integrity and duration of floating (Table 3).
dose of 100 mg of theophylline.After selecting the ideal combination (30:70, drug: polymer), the actual formulations were prepared.The dose of theophylline was taken to be 100 mg.Taking 100 mg as the 30 percent, the quantity of polymers was calculated which came out to be 233.3mg.Four different formulations were prepared using the polymers in different proportions keeping the concentrations of other excipients constant (Table 2).
All the ingredients in the above formulations were weighed accurately and ground individually.All these ingredients were mixed with the drug homogenously and Þ lled in the colorless transparent gelatin capsules.Batch size for all formulations was 100 capsules.The capsules of these formulations were evaluated for buoyancy, matrix integrity, duration of ß oating, weight variation and in vitro drug release characteristics.

TABLE 4 : IN VITRO DRUG RELEASE DATA OF FLOATING CAPSULES OF THEOPHYLLINE
Mean of Triplicate studies.Each capsule contains theophylline 100 mg