INTRODUCTION:

The vesicular carriers were first introduced by Bingham in 1965 and those carriers were named as Bingham bodies.¹But from last two decades, these carriers became prominent in the pharmaceutical field. In these recent years different types of vesicles have been developed which includes liposomes, niosomes, ethosomes, transferosomes, etc. All these vesicular carriers have different specialties either in their composition, morphology or drug delivery mechanism. Researchers have been proved that all these vesicular carriers have many advantages than the conventional drug delivery techniques.

The advantages of these vesicles includes

· Sustained drug delivery,

· Biodegradable and biocompatible.

· Retains in the blood circulation for long period without effecting by the reticulo endothelial system.

· Acts as carriers for both hydrophilic and lipophilic drugs

· Administration is possible from all routes i.e. oral, transdermal, IV, IM, etc.

But, researchers declared that all these vesicles have only one major drawback i.e. physical stability. In order to overcome this drawback, provesicular concept has been introduced.

Under this concept, proliposomes and proniosomes have been studied. Proliposomes concept was first reported by Payne et al.^2,3 This review article deals with advantages, preparation methods, characterizations, and applications of proniosomes.

Proliposomes are composed of water-soluble porous powder as a carrier upon which one may load phospholipids and drugs dissolved in organic solvent. Proliposomes can be stored sterilized in a dry state and dispersed:dissolved in aqueous solution immediately before use which forms an isotonic multilamellar liposomal suspension. It was reported that proliposomes could be stored for longer period without significant changes in distribution of vesicle size and without loss of pharmacological activity than the niosomal suspension.^2,3 Even though proliposome formulations are an improvement over conventional liposome dispersions in terms of the physical stability of the preparation, a vacuum or nitrogen atmosphere is still recommended during preparation and storage to prevent the oxidation of phospholipids.⁴

The stability problems of liposomes are mainly associated with the phospholipids. To avoid these problems it is necessary to change the composition of liposomes by substituting the phospholipids with other ingredients which avoids this stability and other associated technical problems. This was achieved by using non ionic surfactant vesicles in place of phospholipids. On hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or other lipids liposomes like vesicles were formed which were named as ‘niosomes’.⁵

Niosomes are promising vehicle for drug delivery and being non-ionic; it is less toxic and improves the therapeutic index of drug by restricting its action to target cells. These can entrap solutes, are quite stable, and require no special conditions, such as low temperature or inert atmosphere for production or storage. Although the structure and properties of niosomes are similar to those of liposomes, the chemical stability of niosomes and the relatively low cost of the materials that form them make niosomes more attractive than liposomes for industrial manufacturing. However, even though niosomes exhibit good chemical stability during storage, there may be problems of physical instability in niosome dispersions. These niosomes may exhibit aggregation, fusion, leaking of entrapped drugs, or hydrolysis of encapsulated drugs, thus limiting the shelf life of the dispersion. The problems associated with niosomes can be avoided by the proniosomes.

ADVANTAGES OF PRONIOSOMES:

Proniosomes is a dry, free-flowing, granular product which, upon addition of water, disperses or dissolves to form a multilamellar niosomal suspension suitable for administration by oral or other routes. These proniosomes has different advantages.

· Problems associated with aqueous niosomes dispersions and problems of physical stability (aggregation, fusion, leaking) could be minimized.

· Good convenience in the transportation, distribution, storage, and dosing.

· Easy manufacturing.

· All these advantages made ‘proniosomes’ as a good vesicular carrier for drugs.

PREPARATION OF PRONIOSOMES

Proniosomal powder (Slurry method):

A round bottom flask containing small quantity of sorbitol has to be taken and fixed to the rotary evaporator. The surfactant and drug mixture has to be prepared by dissolving in organic solvents like chloroform. The resulting solution has to be introduced in the RBF on rotary evaporator by sequential spraying of aliquots onto the surface of the sorbitol powder. The evaporator has to be evacuated and the rotating flask has to be placed in the water bath at 65-70°C. The flask has to be rotated in the water bath under vacuum for 15-20 min or until sorbitol powder to be dry. Then other aliquots of surfactant solution have been introduced. This process has to be continued until all the surfactant solution has been applied. After addition of final aliquots, the evaporation process has been continued till the sorbitol powder become dry. The material was further dried in desiccators under vacuum at room temperature overnight. The resulting dry powder is said to be proniosomal powder.⁶

Proniosomal gel (Coacervation - Phase separation method):

Drug with surfactant, lecithin and cholesterol were mixed with absolute ethanol in a wide mouth glass tube. Then the open end of the glass tube was covered with a lid and warmed in a water bath at 65±3°C for 5 min. Phosphate buffer(pH 7.4) was added in small quantities and still warmed on the water bath for about 2 min till the clear solution was observed. The mixture was allowed to cool down at room temperature till the dispersion was converted to gel. The resulting gel is referred as proniosomal gel.⁷

CHARACTERIZATION OF PRONIOSOMES:

Surface characteristics:⁸

Surface characteristics include particle size; shape of proniosomal powder and niosomes derived from the proniosomes can be determined by means SEM, TEM, etc analysis.

Flow properties:⁹

Flow properties of the dry proniosomal powder can be determined by finding the densities, angle of repose, carr’s index of the proniosomal powder.

Angle of repose:

Angle of repose can be determined by means of fixed funnel standing method

tan q = h / r

Where, q is angle of repose, h is the height of pile and r is the radius of the pile base.

Bulk and tapped densities:

Bulk and tapped densities of proniosomal powder were measured by using 10 ml of graduated cylinder. The sample poured in cylinder was tapped mechanically for 100 times, then tapped volume was noted down and bulk density and tapped density were calculated.

Carr's index:

Compressibility index (Ci) or Carr's index value of proniosomal powder is computed according to the following equation.

Carr’s index =

[(tapped density – Bulk density)/ tapped density] × 100

Entrapment efficiency:¹⁰

To evaluate the entrapment efficiency, the dry proniosomal powder has to be hydrated with aqueous solution. The resulting niosomal suspension is centrifuzed at 25000 rpm for 30 min at 20°C. The clear supernatant liquid is collected and assayed for un-entrapped drug using HPLC method. The percentage of the entrapment efficiency is calculated by using the following formula.

% entrapment efficiency =

[(Ct – Cf)/Ct] * 100

Where, Ct – concentration of the total drug; Cf - concentration of the free drug.

Rate of spontaneity:¹¹

The number of noisomes eluted from the specific quantity of the proniosomal powder can be determined with the rate of spontaneity test. In this a small specific quantity of dry powder to be taken and hydrated with small volume of the aqueous solution and kept for 20 min for hydration. After 20 min, a drop of niosomal suspension has to be placed on Neubauers chamber and count the niosomes eluted from the proniosomal powder.

In vitro permeation study:¹²

The permeation of drug from noisomes can be evaluated using Franz diffusion cell. Here the franz diffusion cell is mounted with semipermeable membranes like Wister rat skin, etc. The noisomal suspension has to be placed on the donor compartment and phosphate buffer used as receptor medium. Receptor compartment maintained at temperature 37°C and stirred at 600rpm. At regular time intervals the aliquots has to be withdrawn and same quantities are replaced with receptor fluid. The samples were analyzed by HPLC method.

Stability studies:¹³

Stability studies can be performed by exposing the formulations to three different temperatures viz. Room temperature, refrigerated temperature and elevated temperatures.

PRONIOSOMES AS DRUG CARRIERS:

A number of workers have reported the preparation, characterization and use of proniosomes as drug carriers.

Chegjiu Hu, David G Rhodes prepared ibuprofen enclosed proniosomes and niosomes and compared the physical stability such as aggregation, fusion and leaking and other parameters like storage dosing, morphology, particle size, particle size distribution and drug release profile. In all comparisons, proniosomes derived niosomes are shown better than the conventional niosomes.¹⁴

Ibrahim A. Alsarra, AA. Bosela, SM. Ahmed, GM. Mahrous reported that proniosomes are very good tool for transdermal delivery of ketorlac and other drugs by studying the parameters like entrapment efficiency and in vitro drug release profiles of proniosomes derived niosomes.¹⁵

Ankur Gupta et al has prepared proniosomal powder of captopril and examined for various parameters like drug loading, vesicle size, angle of repose, encapsulation efficiency and stability studies and concluded that proniosomes are good choice for preparing stable controlled release dosage form.¹¹

Chandra. A et al formulated proniosomal gel of piroxicam and evaluated for different physical parameters like size, particle distribution, in vitro drug release and in vivo performance and observed that there is significant reduction in inflammation on application of piroxicam proniosomal gel.¹⁶

CONCLUSION:

Vesicular systems are widely accepted by the researchers and academicians in recent days because of its ability to deliver the drug to the desired organs and giving desired activity with less amount of drug with fewer side effects. Among all vesicular systems niosomes has special importance because of its rich quality in different factors like stability, cost, encapsulation capacity, etc. But its importance is limited by its physical instability. This problem can be effectively reduced by the proniosomes concept which was proved by many researchers. As a result of this proniosomes will become prominent drug delivery systems in coming future.

REFERENCES:

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15. Ibrahim A. Alsarra, Bosela. AA, Ahmed SM and Mahrous GM. Proniosomes as a drug carrier for transdermal delivery of ketorlac. European journal of Pharmaceutics and Biopharmaceutics. 2005; 59: 485-490.

16. Chandra A and Sharma PK. Proniosome based drug delivery system of piroxicam. Afr. J. Pharm. Pharmacol. 2008; 2 (9): 184-190.

Received on 15.02.2010 Modified on 25.02.2010

Research J. Pharm. and Tech.3 (3): July-Sept. 2010; Page 709-711