Mixing of Semisolid

Many pharmaceutical products are homogeneous mixtures of two or more

components. Mixing can be defined as a process where two or more components are

treated so as to lie as nearly as possible in contact with a particle of each of the other

components. These may be mixtures of solids, semi-solids, or liquids. Mixtures

containing semi-solids involves incorporating a solid and/or a liquid into a base

consisting of one or more semi-solids. Examples of semi-solids dosage forms include

ointments, pastes and suppositories. Semisolid pharmaceutical systems comprise a

body of products, which when applied to the skin or any accessible mucous

membrane tend to alleviate or treat a pathological condition or give protection to the

applied surface against a harmful environment. Semisolid dosage forms usually are

designed for localized drug delivery. They can be applied topically to the skin, cornea,

rectal tissue, nasal mucosa, vagina, buccal tissue, urethral membrane, and external ear

lining. One of their properties for them to exert their therapeutic effect is semi solids

pharmaceutical systems able to cling to skin or mucous membrane for a protracted

period of time due to their plastic rheologic behavior.

The general method of processing semisolid pharmaceuticals products i.e.

creams, jellies and ointments consists of three-step batch operation. A hot oil phase

and a hot aqueous phase are brought together, thoroughly mix to cause the two phases

to form a substantially homogeneous mixture and then cooled until the homogeneous

mixture congeals and forms semisolids products. However, restricted production time

and extensive material handling are two inconveniences of this method. Therefore, in

accordance with present invention, a process for preparing semisolid dispersions is

provided which can be carried out continuously and which is substantially more

efficient than the previous method. The process of the present invention comprises
combining the two immiscible phases in one vessel and circulating the mixture

through a system of mixers and/or homogenizers until the desired homogeneity is

achieved. The major problem which arises during the mixing of semisolids is

semisolids will not flow easily. Material that finds its way to ‘dead’ spots will remain

there. For that reason suitable mixers must have rotating elements with narrow

clearances between the mixing vessel and they must produce a high degree of shear

mixing since diffusion and convective mixing cannot occur.

There are two mixers for semisolids which are the Planetary Mixer and the

Sigma Blade Mixer. For planetary mixer, this mixer is suitable for powder mixing and

also mixing of viscous liquid. The mixer is named ‘planetary’ because the paddle is

impeller blades that rotate on its own axis also travels in a circular path round the

mixing vessel in opposite direction. In the Planetary Mixer, a small clearance between

vessel and the paddle gives shear but “scraping down” several times is necessary to

mix the contents well since some materials are forced to the top of the bowl. The

blade will continuously advance along the periphery of the vessel, removing material

from the vessel wall and transporting it to the interior.

In the other hand, the Sigma Blade mixer, the robust mixer will deal with stiff

pastes and ointments and depends for its action on the close intermeshing of the two

blades which resemble the Greek letter sigma (∑) in shape. For the Sigma Blade

mixer, it is engineered specifically for kneading, mixing and homogenizing wet,

pasty, and highly viscous products. It contains two Sigma (∑) shaped blades, which

sit horizontally and parallel at the bottom of the mixing trough. The blades will rotate

at different speeds in opposite directions. This will cause the product to be transferred

from blade to blade and from end to end, resulting in a figure eight pattern and also

for efficient kneading of paste.

 Many pharmaceutical products involve in the process of mixing semisolid.

Semisolid includes ointments, creams, pastes, gels, kaolin suppositories, poultice and

also plaster and rigid foam. Ointments are greasy preparations, gels are transparent or

translucent, non-greasy, aqueous preparations. For examples, ointments can be

prepared as topical antiseptic, antifungal, or antibacterial preparations which include

sulphur ointment, Ichthammol ointment, and also Whitfield’s ointment. Plasters are

solid or semisolid masses that adhere to the skin when spread upon cotton felt line or

muslin as a backing material. They are mainly used to afford protection and

mechanical support, furnish an occlusive and macerating action and bring medication

into close contact with the surface of the skin. Pastes contain a higher proportion of

finely powdered medicament compared to ointments or gels, for example: Zinc and

coal tar paste that is used as antipruritic preparation.

In addition, mixing of semisolids has its own advantages and also

disadvantages. Advantages of semisolids mixing include mixing can be rapid in

uniform temperature and concentrations, it is applicable for large or small scale

operations, heat and mass transfer are high, and the process is easy to control due to

stable conditions. However, the process brings some disadvantages which include fine

particles are difficult to predict and less efficient and also present of non-uniform flow

patterns. Semi solids unlike powders and liquids, they are not easy to flow.

The current invention of semisolids products are non greasy since they are

made up of water washable bases. This can cause less irritation to skin and are

superior to conventional semisolid dosage form. Creams nowadays are provided with

nanoparticles and microspheres, which has an excellent emollient effect, with better

spreadability, and less staining than oleaginous ointments. Number of innovation is

carrying out in gels in terms of modification of release pattern and also some
thermoreversible gels have been carried out in research. Complex gels for Ora/ Insulin

delivery, chitosan based bioadhesive gels and TIMERx technology for controlled

release, amphiphilic and non-aqueous gels are also the latest innovations in gel

formulations. Foams are normally easier to apply, less dense, and spread more easily.

In the future, foams may be designed in ways to provide emollient or drying functions

to the skin, depending on the formulation constituents. Although there is not enough

clinical evidence that foam formulations can be well developed, these formulations

show clear application advantage and continued developments in the science of

supersaturating technology will be carried out.

There are certain limitations on this process. In semi-solid base, it is very

difficult using primary mixers to completely disperse powder particles so that they are

invisible to the eye. Rub out particles by the intense shear generated by rollers or

cones set with a very small clearance between them. Suspensions or pastes containing

high proportion of solids often develop high apparent viscosities at high rates of shear

(dilatants flow) so that high speed mixers would be unsuitable. For paste showing

plastic properties, yield stress must be reached before the material starts to flow so

that a substantial force must be applied before any motion takes place. As plastic

solids have very limited flow, better mixing can be obtained by forcing the particles

of one constituent between the particles of the other constituents.

References:

http://www.mixers.com/Proddetails.asp?ProdID=58

http://www.freepatentsonline.com/5145095.html

http://www.pharmainfo.net/search/node/Novel%20Semisolid%20Dosage%20Forms
The Planetary Mixer
Sigma Blade Mixer