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ORIGINAL/BRIEF
Year : 2012  |  Volume : 4  |  Issue : 5  |  Page : 95-97  

Formulation and evaluation of transparent ibuprofen soft gelatin capsule


Gujarat Liqui Pharmacaps Pvt. Ltd., 662-666, GIDC, Waghodia, Baroda, Gujarart, India

Date of Web Publication21-Mar-2012

Correspondence Address:
A Lodha
Gujarat Liqui Pharmacaps Pvt. Ltd., 662-666, GIDC, Waghodia, Baroda, Gujarart
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-7406.94154

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   Abstract 

The compound ibuprofen, 2-(4-isobutylphenyl) propionic acid, has been known e.g. from Martindale, the Extra Pharmacopoeia, 28 th edition, 1982, p.256, as a drug which had anti-inflammatory and analgesic properties. It is used for the treatment of rheumatoid arthritis or other inflammatory diseases of joints, soft tissue rheumatism and gout. Ibuprofen, because of its analgesic properties, has been widely used as anodyne, e.g. against pain or discomfort associated with headache, toothache or menstruation.
A medication suitable to combat acute pain is demanded to display its effects fast which action, in turn, is only achieved by a quick release and good bio-availability of the active-ingredient. It is for the commercial forms in particular that the conditions of preparation must be strictly observed, as minor alterations in production procedures such as mixing, pressure of compression and type of machine will affect the physical properties of the particles of he active ingredient and will deteriorate its bio-availability. It is an object of this presentation to provide a medicament that can be readily taken that contains an active amount of ibuprofen in a carrier, that is simple to prepare and that will quickly display a high activity.

Keywords: Ibuprofen, anti-inflammatory


How to cite this article:
Lodha A, Patel A, Chaudhuri J, Jadia P, Joshi T, Dalal J. Formulation and evaluation of transparent ibuprofen soft gelatin capsule. J Pharm Bioall Sci 2012;4, Suppl S1:95-7

How to cite this URL:
Lodha A, Patel A, Chaudhuri J, Jadia P, Joshi T, Dalal J. Formulation and evaluation of transparent ibuprofen soft gelatin capsule. J Pharm Bioall Sci [serial online] 2012 [cited 2020 Sep 25];4, Suppl S1:95-7. Available from: http://www.jpbsonline.org/text.asp?2012/4/5/95/94154

Formulation development

Vehicle

Compound that show low aqueous bio-availability have the tendency to precipitate when small amounts of water is added to the solution, thus affecting its resorption. This can be overcome by the addition of combination of Hydrophilic vehicles. Hydrophilic vehicles for softgel fill formulations include polyethylene glycols (e.g., PEG 400, PEG 600), polyoxyethylene - polyoxypropylene copolymers (Poloxamers), propylene glycol, glycerin, ethyl alcohol, and water. The use of propylene glycol, glycerin, and water is restricted to less than 10% of the total fill formulation, as these vehicles can also act as plasticizers for the gelatin shell. Similarly, use of lower molecular weight polyethylene glycols (e.g., PEG 200, PEG 300) in the fill formulations is limited due to their ability to diffuse into the shell and thereby act as gelatin plasticizers. The extent of diffusion of a polyethylene glycol from the fill into the shell decreases with an increase in its molecular weight. Orally administered polyethylene glycols of a lower molecular weight (e.g., PEG 200, PEG 300, PEG 400) are well absorbed in the GIT and are mostly (>90%) excreted unchanged in urine and feces in human subjects.

Solubility enhancers

It is desirable to produce a highly concentrated solution of a compound as it allows the encapsulation of a unit dose of the compound in a softgel that is small enough to swallow easily and thus improving patient acceptance of the medication. The solubility of the acidic compounds like ibuprofen can be enhanced in polyethylene glycols by 40-400% through partial ionization of this compound with a hydroxide ion species (e.g., sodium hydroxide, potassium hydroxide, ammonium hydroxide). When this neutralization (counter ion) technique is used to obtain a highly concentrated solution of a compound, it is essential to keep the apparent pH of the final fill formulation at least between 2.5 and 7.5. At pH values below 2.5, gelatin is hydrolyzed causing leakage of the softgel, whereas at pH values above 7.5, gelatin may be either hydrolyzed or tanned (i.e. cross-linked) resulting in decreased solubility of the gelatin shell.

Alternately, the solubility of ibuprofen in hydrophilic vehicles can also be improved significantly by using povidone (polyvinylpyrrolidone, PVP) as a solubility enhancer. Unlike the solubility enhancing techniques employed the use of povidone as a solubility enhancer results in a softgel fill formulation containing a compound in its original form that is very compatible with the other softgel components. In addition, as povidone is available in a variety of molecular weights ranging from 2500 to 3000000 the viscosity of a fill formulation can be controlled through the selection of appropriate molecular weight and concentration of the polymer without adversely affecting the solubility of dissolved compounds.


   Materials and Methods Top


Ibuprofen (active ingredient), polyethylene glycol 400 (vehicle), polyvinyl pyrrolidone (K-10) (solubility enhancer), polyethylene glycol (co-solvent), potassium hydroxide (ionizing agent).

Optimization of fill material

In order to obtain the optimized fill formulation, ibuprofen is initially dissolved in 15 to 50 parts of polyethylene glycol along with 2 to 50 parts of polyethylene glycol which is then mixed with polyvinyl pyrrolidone K-30. The previously mixed potassium hydroxide with water is added till optimum pH is obtained.

Encapsulation parameter



Evaluation of ibuprofen soft gelatin capsules

Uniformity of fill weight of the capsules

Weigh an intact capsule. Open it without losing any part of the shell and remove the contents as completely as possible. Wash the shell with a suitable solvent and keep aside until the odor of the solvent is not perceptible. Weigh the shell. The difference between the weighing gives the weight of the contents. Repeat the procedure with another 19 capsules. The weight complies as per the pharmacopoeial limits.

Loss on drying of the capsule shell

Soft gelatin capsule shells normally contain 6% to 13% of water and the Loss on Drying of the shell was found to be within the limit.

Disintegration test for soft gelatin capsules



Although there are no official limits specified, ideally a disintegration time within 30 minutes is considered ideal for soft gelatin capsules. The formulated capsules disintegrated within a maximum of about 25 mins as shown in the table.

Dissolution studies of ibuprofen soft gelatin

Ideal media for dissolution study was optimized from the disintegration test prior to dissolution testing studies. Various Gastric stimulated media for dissolution were 0.1N HCl (pH 1-2), acetate buffer (pH 4.5), phosphate buffer (pH 7.8) and water. The dissolution media consisting of Phosphate Buffer Solution at pH 7.8 provided best cumulative drug release as depicted in graphs.

Assay

Experimental chromatographic conditions

Stationary phase: Phenomex, 5 μm, C18 (250x4.6 mm) column

Mobile phase: A mixture of 3 volumes of orthophosphoric acid, 247 volumes of water and 750 volumes of methanol

Detection wavelength: 264 nm

Flow rate: 1.5 ml/minute

Operating pressure: 160 kgf

Temperature: Room temperature.

Preparation of standard solution:

100 mg of Ibuprofen diluted with the Mobile phase up to 100 ml (Stock Solution).

Make 100 μg/ml of Ibuprofen diluted with the Mobile phase.

Aliquots of standard solutions containing 40 μg/ml of Ibuprofen.

Preparation of sample solution:

20 tablets → Average weight → Powdered and weighed a quantity equivalent to 100 mg of Ibuprofen were transferred to 100 ml standard flask and make up with mobile phase. Filter with Whatman filter paper.[Figure 1], [Figure 2].
Figure 1: Optimization of dissolution media

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Figure 2: Comparative dissolution studies of developed formula and marketed product

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Aliquots of solution containing 40μg/ml diluted with mobile phase.

Analysis of formulation




   Conclusion Top


The soft gelatin dosage form has an advantage over all other previously known dosage form for ibuprofen that upon intake the active ingredient is quickly resorbed. Nevertheless, by employing the above mentioned techniques, a high-bioavailability is achieved with a high degree of reliability and reproducibility and hence, a fast and reliable display of its effects. [4]

 
   References Top

1.Brox W. 1988. Soft gelatin capsules and methods for their production. US Patent 4,744,988.  Back to cited text no. 1
    
2.Brox W. 1988. Gelatin capsule. US Patent 4,780,316.  Back to cited text no. 2
    
3.Nazzal S, Wang Y. 2001. Characterization of soft gelatin capsules by thermal analysis. Int J Pharm 230:35-45.  Back to cited text no. 3
    
4.Dhabhar DJ. 1996. Process for reducing the precipitation of difficulty soluble pharmaceutical actives US Patent 5,484,606.  Back to cited text no. 4
    


    Figures

  [Figure 1], [Figure 2]


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[Pubmed] | [DOI]



 

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