JPH0316635A - Production of w/o/w type composite emulsion - Google Patents

Abstract

PURPOSE:To obtain W/O/W-type composite emulsion having high stability by preparing a mixture system of an oil phase containing nonion surfactant and a water phase containing hydroxypropyl cellulose, and emulsifying this mixture near the temp. at which hydroxypropyl cellulose does not melt. CONSTITUTION:Hydroxypropyl cellulose(HPC) is used as a hydrophilic emulsifier. As for a lipophilic emulsifier, noion surfactant such as sorbitane ester is used. When the mixture of an oil phase and an water phase containing these emulsifiers is emulsified near the temp. for stable HPC, adsorption on the interfaces of HPC is promoted and the system is stabilized. Further, the system is processed at >=0.05ml sec shear rate to obtain a fine emulsion. Thereby, the obtd. emulsion has high productivity and stability.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing a W/O/W type composite emulsion. Specifically, using hydroxypropyl cellulose and a nonionic nasal surfactant as an emulsifier,
The present invention relates to a method for producing a W/O/W type composite emulsion with excellent stability by carrying out emulsification at a specific temperature and at a fixed shear rate.

[Conventional technology]

W/O/W type composite emulsions are widely used in drug delivery systems in the pharmaceutical field, as bases for liquid membranes in membrane separation, and in the food and cosmetics fields.

A method for producing a W/O/W type composite emulsion is an example in which nrubitan monooleate is used as a lipophilic emulsifier and sodium dodecylbenzenesulfonate is used as a hydrophilic emulsifier, instead of the above-mentioned sodium dodecylbenzenesulfonate. Examples using hydrophilic emulsifiers such as cetyltrimethylammonium bromide or polyoxyethylene sorbitan monooleate are known (S. Matsumoto
, J. Colloid Interface Set
．． ．． 917. 34;2(/9;3)). In addition, there is a known example in which a composite emulsion By was prepared using biological substances isolated from bacteria (J.
Chandrakante. al + J. Co
lloid Interface Sci. , i1
, 295 (/?ku 9)) 0 [Problem to be solved by the invention] However, when using a low molecular weight emulsifier as mentioned above, the stability of the W/O/W type composite emulsion is poor and 9, which resulted in a W/O or 0/W type emulsion, had the disadvantage that it separated into two phases upon coalescence.

[Means to solve the problem]

That is, the present invention uses hydroxypropyl cellulose as a hydrophilic emulsifier and a nonionic surfactant as a lipophilic emulsifier, and a mixed system of an oil phase and an aqueous phase containing the emulsifier is heated to a temperature close to the insolubilization temperature of hydroxypropyl cellulose. Under the temperature of 0. The gist of the present invention is a method for producing a W/0/W type composite emulsion, which is characterized by carrying out emulsification at a shear rate of 0 3 m/sec or higher.

Hydroxypropyl cellulose (hereinafter abbreviated as 1-HPCJ) used as a hydrophilic emulsifier in the present invention has a molecular weight of 30,000 to 700,000, and 4I to 6 of the OH groups in the repeating structural unit in cellulose. HPC has a structure represented by the general formula below and is substituted with a hydroxyprobyl group (0 (m is an integer of /~S)) HPC generally becomes insoluble in water when an aqueous solution is heated. It has the property of precipitating. In the present invention, an aqueous solution of a predetermined concentration is gradually heated, and the temperature at which the system becomes cloudy is defined as the insolubilization temperature (LCST').

The amount of RPC used is O. θOj~θ. l
Heavy weight, good bite and pao. θ/~0. θS weight is a problem.

The lipophilic emulsifier used in the present invention includes a nonionic surfactant, preferably a nonionic surfactant with an HLB of 7 or less, for example, sorbitan esters such as sorbitan monostearate and sorbitan monooleate; Examples include ethylene oxide adducts of higher alcohols and block copolymers of propylene oxide and ethylene oxide. These nonionic surfactants are suitable for oil phase! -50 weight range, preferably /θ
It is used in the range of ~3s weight flies.

The oil phase forming the W/O/W emulsion may be any organic liquid that is incompatible with water, such as liquid paraffin, paraffin wax, hydrocarbons such as decane and n-hexane, and palm oil. , fats and oils such as cottonseed oil and beef tallow, organic solvents such as toluene, benzene, esters, and ketones, various higher alcohols, liquid polymers such as liquid polybutene, and silicone oil.

A method for producing a W/O/W type emulsion includes a phase inversion method in which an aqueous phase containing HPC is gradually added dropwise to an oil phase containing a nonionic surfactant under stirring to invert the phase;
There is a one-step method of mixing the aqueous phase and both emulsifiers, but in these methods, the rules for combining the inner aqueous phase and the outer hydration are the same. Therefore,
When changing this composition, a two-step method is used in which a W/O emulsion is prepared in the first step, and then the emulsion is dispersed in the outer aqueous phase.

In any emulsification system, when emulsification is carried out at a temperature near the LCST of HPC, preferably in the temperature range of LCST-/θ°C to LCST+S'c, and more preferably in the temperature range of LCST, t°C to LCST+s'c, the It is necessary to carry out the emulsification at this temperature because adsorption is promoted and the system is further stabilized.

On the other hand, in a conventional system using only a surfactant, the composite emulsion will break if the stirring intensity is high, but in the system of the present invention using HPC, on the contrary, the shear rate is 0-0.
! ; m/sec N, preferably θ. / m/se
Since it is not possible to obtain a sufficiently fine emulsion unless the stirring is at least 0. 0! It is necessary to perform emulsification at a shear rate of rm/see or higher.

Other substances in the oil phase or aqueous phase formed in the present invention,
For example, it is possible to contain pharmaceuticals and the like. Cabinet,
It is also possible to use a surfactant in combination.

[Examples] Next, the present invention will be described in more detail with reference to Examples and Comparative Examples. In addition, in the example below!笀 and 1 means "parts by weight" and "parts by weight", respectively.

The measured molecular weight of LCST is 30,30,000, and the degree of substitution is 30,000. When a 0.0/% aqueous solution of hydroxypropylcellulose was gradually heated from room temperature and the temperature at which it became cloudy was measured, it was 7°C. 72
Put 0tst and 0.0/% aqueous solution of HPC gOmt into a 200-cm glass beaker and bring the internal temperature to lI! Raise the temperature to f°C and use a propeller blade type stirrer with a diameter of 3θ■φ at that temperature! rkO rpm (/...?Xlθ-'
m/sec) to obtain a W/O/W type composite emulsion.

The survival rate and stability of the obtained composite emulsion are shown in Table 1. Example 2 n-Hebutane lI containing 30 doses of sorbitan monooleate
o- and HPC θ. θ/% aqueous solution/01 was placed in a 300° glass beaker, the internal temperature was raised to 1IS°C, and at that temperature, using the same stirrer as in Example/! r k O
A water-in-oil (W/O) type emulsion was prepared by emulsifying the mixture at rpm. Then, 200°C of a 0.0/φ aqueous solution of RPC (kept at 30°C) was added to the mixture at r30
The mixture was emulsified at rpm to obtain a W/O/W type composite emulsion.

The production rate and stability of the resulting composite emulsion are shown in Table 0. Emulsification was carried out in the same manner as in Example/, except that the temperature in Comparative Example/Example/ was set to room temperature (approximately .2 rt). A W/O/W type composite emulsion was obtained.

The production rate and stability of the obtained composite emulsion are shown in Table 1.

In Comparative Example and Example, the stirring number was set to t 30 rpm (3
．． Emulsification was carried out in the same manner as in Example 1, except that g I couldn't.

Comparative Example 3 Same as Example 2 except that a nonionic surfactant (sorbitan monooleate ethylene oxide adduct: Tween 1; θ) solution was used instead of the RPC aqueous solution. and emulsify W/0/W
A type composite emulsion was obtained.

The production rate and stability of the obtained composite emulsion are shown in Table 1.

Table 7 l) The particle size distribution of the obtained composite emulsion was determined by image processing from a microscopic photograph, and the abundance of particles larger than gμ was defined as the proportion of the W/O/W composite emulsion.

2) By microscopic observation after being left for 7 days, items with almost no change are rated ○, items with considerable damage are Δ, and completely O/
Items that were W-type emulsions were marked as ×.

〔Effect of the invention〕

The W/O/W type composite emulsion produced by the method of the present invention has a higher production rate and extremely good stability compared to those obtained by conventional methods.

Mitsubishi Kaoru Co., Ltd.

Claims (1)

[Claims] (1) Hydroxypropylcellulose is used as a hydrophilic emulsifier and a nonionic surfactant is used as a lipophilic emulsifier, and a mixed system of an oil phase and an aqueous phase containing the emulsifier is heated at a temperature near the insolubilization temperature of hydroxypropylcellulose. 0
．． A method for producing a W/O/W type composite emulsion, characterized in that emulsification is carried out at a shear rate of 0.5 m/sec or more.