Hard Capsules: A Suitable Alternative to Soft Gelatin Capsules for Delivering Liquid Drugs

 

Bhutkar MA1*, Yadav AV2, Sevukarajan M2 and Sonawane RO2

 

1*Rajarambapu College of Pharmacy, Kasegaon, Dist Sangli. (M.S) 415 404.

2Govt. College of Pharmacy, Karad. (M.S) 415 124.

* Corresponding Author E-mail: mangesh_bhutkar@rediffmail.com

 

ABSTRACT

Liquid filled soft gelatin capsules have been successfully used for delivering a variety of liquid drugs. However, these soft capsules possess certain drawbacks. The important one is the in-house development and manufacturing is difficult and costlier. The filling of liquids into hard gelatin capsules may help to overcome the drawbacks and offer added advantages. In the present study attempts have been made to design and develop liquid filled hard gelatin capsules and to evaluate and compare their suitability for liquid filling with marketed soft gelatin capsules. Thus, the purpose of the study was to know whether hard capsules could act as a suitable alternative to soft capsules for delivering liquid drugs.

 

KEY WORDS Hard Capsules, Soft capsules, vitamin E, formulation.

 

INTRODUCTION:

Capsules afford a tasteless, odorless enclosure convenient for administration of variety of medicaments, which are otherwise difficult to administer. The filling of liquid drugs, molten or thixotropic liquids into capsules may be used  to  overcome a  number of  problems, which are frequently associated with the development, and manufacture of conventional pharmaceutical capsules1. Soft gelatin capsules have been preferred for liquid filling. However, they possess certain drawbacks such as high oxygen permeability, greater risk of drug migration for plasticizer soluble drugs and variations in capsule dimensions. Moreover, the in-house development and manufacturing is difficult and due to the complexities of the process, very few pharmaceutical companies get involved in this operation2. On the other hand, the technology of filling liquids into hard capsules can be brought in-house which requires simple machine and relatively small amounts of material for filling trials3. The hard  capsules exhibits low moisture uptake  and  thus avoid the migration and degradation of moisture sensitive drugs4. Due to low permeability of capsule wall, the hard capsules could be used for filling of oxygen sensitive drugs. Moreover the amount of gelatin used for a hard capsule shell is less than for soft capsule shell thus, it is cheaper and economic as well.

 

For these reasons the use of hard capsules for liquid filling is more justifiable than soft capsules. Vitamin E filled soft gelatin capsules are available in market. But if the cost of the preparation could be minimized by filling it into hard gelatin   capsules   it   may   offer   an   added   advantage. Moreover, by formulating different formulations of vitamin E  and  studying their  drug release from  hard  capsules a suitable alternative to vitamin E filled soft gelatin capsules can be achieved.

 

MATERIALS AND METHODS:

Vitamin E was procured from USV Ltd, Mumbai, hard capsules size “0” from ACG, Transcutol P, Labrafac CC, Tween 80, PEG were procured from Colorcon Asia Pvt. Ltd. Purified Pepsin was obtained from Loba Chemie Pvt. Ltd. Mumbai. Cornstarch and Bees-wax from Swastik Pharmaceuticals. Purified Talc from Apex Pharmaceuticals and Spermaceti was procured from Amrut Pharmaceuticals, Mumbai.

 

Formulations of Vitamin E

Formulation I-  Self-micro  emulsifying formulation of Vitamin E5.

This formulation comprised of Vitamin E 46.5%, Labrafac CC  46.5%,  Transcutol P  2.32%,  and  Tween  80  46.5%. Vitamin E was dissolved in measured quantity of Labrafac CC (oil). Accurately measured quantities of Tween 80 (surfactant)  and  Transcutol  P  (co-surfactant)  were  then added to obtain a clear, transparent self-micro emulsifying formulation of Vitamin E. The prepared self-micro emulsifying formulation of Vitamin E was characterized by visual  observation  for  transparency  and thermodynamic stability was evaluated by subjecting the micro emulsion to centrifugation at 5000 rpm for 20 min.

 

Table 1: Cumulative Percent Release of Various Formulations of vitamin E filled Hard Capsules and Marketed vitamin E Filled Soft Gelatin Capsule

Time (min)	Cumulative Percent Release of formulations filled in Hard capsules						Cumulative Percent Release from Marketed Soft Gelatin capsule
	Formulations
	I	II	III	IV	V	VI
0	0	0	0	0	0	0	0
5	39.095	4.468	35.770	3.083	9.731	2.806	3.152
10	40.350	4.839	37.631	3.446	26.475	4.622	4.017
15	45.560	5.974	43.587	4.296	36.592	5.617	4.854
20	52.459	8.846	47.428	5.359	41.921	8.072	8.828
30	71.376	9.933	67.356	6.358	81.973	11.025	25.359
40	94.136	27.440	77.282	7.570	91.636	32.831	55.694
50	96.382	30.846	87.608	12.043	96.640	65.493	89.036
60	98.201	39.465	91.617	18.619	97.384	73.542	96.746
70	99.620	52.493	94.469	25.508	99.294	96.454	99.054

 

Formulation  II-  Thermal  setting  formulation  of Vitamin E6.

This formulation comprised of Vitamin E 40 %w/w and PEG 60 %w/w. PEG was heated and stirred on water bath and Vitamin E was added and mixed thoroughly. Hot melt was then filled into capsule shells.

 

Formulation III- Formulation of Vitamin E with Bees-wax and Spermaceti.

This formulation comprised of Bees-wax 10%, Spermaceti 12%, Vitamin E 53%. Bees-wax and Spermaceti were heated and stirred on water bath and Vitamin E was added and mixed thoroughly. The hot melt was then filled into capsule shells. After filling the capsules were allowed to cool to room temperature so that melt is solidified. The capsules were then sealed.

 

Fig. 1: Release Profile of vitamin E from Soft Capsule (Marketed Formulation) and Hard Capsules filled with various formulations of Vitamin E

 

Formulation IV- Vitamin E adsorbed on Talc.

In a mortar 225 mg of Talc was taken and 200 mg of Vitamin E was added to it in small quantities with constant trituration so that Vitamin E is adsorbed on Talc.

 

Formulation V- Vitamin E adsorbed on Cornstarch.

In a mortar 225 mg of Cornstarch was taken and 200 mg of Vitamin E was added to it in small quantities with constant trituration so that Vitamin E is adsorbed on Cornstarch.

 

Formulation VI- Vitamin E filled hard gelatin capsules.

Hard gelatin capsules containing 200 mg of Vitamin E were prepared by filling Vitamin E as such without any excipient into these capsules.

 

The prepared formulations were filled in hard gelatin capsules and they were sealed using a hydro-alcoholic solution. The various stages of the sealing process were as follows7.

 

•      Moisturizing:  In  this  stage  a  50:50  water/ethanol mixture was applied on to the joint. The excess fluid was removed by using a cotton swab.

•       Warming: Application of gentle heat of approximate 45°C enabled the fusion of two gelatin layers to form a complete 360° seal.

•      Setting:  Gelatin  setting  or  hardening  process  was completed  while  the  product  attained  room temperature.

 

Dissolution rate studies8

The drug release study from hard capsules was carried out using USP (Veego DA-6D) dissolution rate test apparatus. The dissolution studies were performed at 37±0.50C using one  capsule  at  a  time  in  a  basket  at  100  rpm.  The dissolution media used was simulated gastric fluid. During the test 5 ml of aliquot was withdrawn at specified time intervals. After each withdrawal, dissolution medium was replaced  with 5  ml  of  same  dissolution medium having same  temperature.  Each  5  ml  withdrawn  sample  was filtered through Whatmann’s filter paper and absorbance of filtered solution was measured at 284 nm. Drug concentration at each stage in the samples was determined from respective calibration curve. Percent cumulative release of each formulation was then reported.

 

RESULTS AND DISCUSSION:

Amongst the formulations of Vitamin E, filled in hard gelatin capsule, the four formulations (Viz. I, III, V, VI) showed the expected drug release profile. Remaining two formulations (Viz. formulation II and IV) showed very slow and poor drug release. Vitamin E release from hard gelatin capsule is comparable to that  shown  by  marketed  soft  gelatin  capsule  of Vitamin E.

 

CONCLUSION:

Our results indicate that hard gelatin capsules can be conveniently and effectively used for delivering Vitamin E. And as compared to soft gelatin capsules this drug delivery system would prove more cost effective

 

REFERENCES:

1.     Patro GP, and Rao CG. Novel Approach: Liquid filled Hard Gelatin Capsules. The Pharma Review. 2003; 85-86.

2.     Ghirardi PA, Catenazzo GC and Mantero OS. Bioavailability of Digoxin in a New Soluble Pharmaceutical formulation in Capsules. Indian J Pharm Sci. 1977; 66(2): 267.

3.     Hawley AR. et al. Physical and chemical characterization of thermo softened bases for molten filled hard gelatin capsule formulations. Drug. Dev. Ind. Pharm. 1992; 18(16):1719.

4.     Armstrong NA, et al. Drug migration into soft gelatin capsule shells and its effect on in vitro availability. J Pharm Pharmacol. 1984; 36:361.

5.     Howard JR and Gould PL. Drug release from thermosetting fatty  vesicles  filled  into  hard  gelatin  capsules.  Drug  Dev. Ind. Pharm. 1987; 13 (6):1031-1040.

6.     Walker SE, et al. The filling of molten and thixotropic formulations in to hard gelatin capsules. J Pharm. Pharmacol. 1980; 32:389.

7.     Cade DA, et al. Liquid filled and sealed hard gelatin capsules. Acta. Pharm. Tech. 1987; 33(2): 97.

8.     United States Pharmacopoeia, XXIV, NF XIX, The USP Convention, Inc, Rockville, MD. 2000:1732.

 

Accepted on 03.08.2008   © RJPT All right reserved