常用软膏剂的制备

常用软膏剂的制备

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Preparation of ointments

Ointments are semi-solid preparations made of medicaments and suitable bases, which are intended for external application to the skin. Ointment bases recognized for use as vehicles distinguished into three general classes: the oleaginous bases, the emulsion bases, and the water –soluble bases.

There are three general methods: the method of grinding and mixing, the method of melting and mixing, the method of emulsification.

Ophthalmic ointments are ointments for application to the eye whose bases general include liquid paraffin, Vaseline and wool fat. Special precautions must be taken in the preparation of ophthalmic ointments. They are manufactured from sterilized ingredients under rigidly aseptic conditions. The ointment base that is selected must be without any irritation to eye.

Equipments:

evaporating, water bath, electric furnace, analytical balance, thermometer, microscope etc.

Materials:

Stearic acid, glycerol monostearate, Vaseline, glycerol, liquid paraffin, triethanolamine, calcium hydroxide, CMC-Na, span80, nonoxynol-10, distilled water etc.

Procedures:

1. O/W emulsion base

Formulation

Stearic acid 4.8g

Glycerol monostearate 1.4g

Liquid paraffin 2.4g

Vaseline 0.4g To keep water

Wool fat 2.0g

Triethanolamine 0.16g

Distilled water add up to 40.0g

Preparation:

Add stearic acid, glycerol monostearate, liquid paraffin, Vaseline and wool fat into evaporating dish, which the mixture is used as oil phase. Add triethanolamine and distilled water into beaker, which the solution is used as a water phase. The two containers are heated to 80°C in water bath and kept until melting completely. Pour oil phase into water phase slowly, and stir them fully. Cool at room temperature, then the O/W emulsion base can be got.

2. W/O emulsion base

Formulation:

Glycerol monostearate 0.85g

Beeswax 5.25g

Paraffin 3.75g

Stearic acid 0.625g

Liquid paraffin 20.5g

Vaseline 3.35g To keep water

Span80 0.5g

calcium hydroxide 0.05g

Ethylparaben 0.1g

Distilled water 10.0g

Essence 2 drops

Preparation:

Add glycerol monostearate , paraffin and stearic acid into the evaporating dish that is above water bath. When the mixture is melted, add Vaseline, liquid paraffin and aluminum distearate into it. The above mixture is used as the oil phase. Calcium hydroxide and ethylparaben are dissolved in distilled water. The degree of water is about 80°C.The solution is used as the water base. A clockwise stirring is needed when add water phase into oil phase. Cool the base to the room temperature, then the W/O emulsion base can be got.

Results and Discussion:

The first O/W is a kind of thick white ointment, while the second is a bit yellow, and the former is thin than the latter. Both the two products have a kind of smell.

In the preparation of ointments ,we should keep the temperature at 80°C for the reason of getting the reaction started. And the temperature of the water phase should be higher than that of the oil phase, under this condition, we can make sure

that the oil phase and the water get in touch and have a complete reaction.

The experiment is considered to be a successful one .

References:

软膏剂（Ointments）

软膏剂（Ointments）指药物与适宜基质均匀混合制成的具有一定稠度的半固体外用制剂。常用基质分为油脂性、水溶性和乳剂型基质，其中用乳剂基质制成的易于涂布的软膏剂称乳膏剂。

因药物在基质中分散状态不同，用溶液型软膏剂和混悬型软膏剂之分。溶液型软膏剂为药物溶解或共熔于基质或基质组分中制成的软膏剂，混悬型软膏剂为药物细粉均匀分散与基质中制成的软膏剂。

软膏剂基质可分为油脂性基质和水溶性基质。油脂性基质常用的有凡士林、石蜡、液体石蜡、硅油、蜂蜡、硬脂酸、羊毛脂等，水溶性基质主要有聚乙二醇。

乳膏剂：系指药物溶解或分散于乳状液型基质中形成的均匀的半固体外用制剂。乳膏剂由于基质不同，可分为水包油型乳膏剂和油包水型乳膏剂。

乳膏剂常用的乳化剂可分为水包油型和油包水型。水包油型乳化剂有钠皂、三乙醇胺皂类、脂肪醇硫酸（酯）钠类（十二烷基硫酸钠）和聚山梨酯类；油包水型乳化剂有钙皂、羊毛脂、单甘油酯、脂肪醇等。

软膏剂和乳膏剂基质应均匀、细腻，涂于皮肤或黏膜上应无刺激性，混悬型软膏剂中不溶性固体药物应预先用适宜的方法磨成细粉，确保粒度符合规定。

软膏剂和乳膏剂根据需要可加入保湿剂、防腐剂、增稠剂、抗氧剂及透皮促进剂。

软膏剂和乳膏剂应具有适当的粘稠度，应易涂布于皮肤或粘膜上，不融化，粘稠度随季节变化应很小。

软膏剂和乳膏剂应无酸败、异臭、变色、变硬，乳膏剂不得有油水分离及胀气现象。

除另有规定外，软膏剂应遮光密闭保存，乳膏剂应遮光保存，宜置25℃一下贮存，不得冷冻。

除另有规定外，检验一下项目：

【粒度】除另有规定外，混悬型软膏剂取适量的供试品，涂成薄层，薄层面积相当于盖玻片面积，共涂三片，照药典粒度和粒度分布测定法检查，均不得检出大于180μm的粒子。

【装量】照药典最低装量检查法检查，应符合规定。

【无菌】用于烧伤或严重创伤的软膏剂与乳膏剂，照药典无菌检查法检查，应符合规定。

【微生物限度】除另有规定外，照药典微生物限度检查法检查，应符合规定。

Ointments

Ointments are used topically for several purposes, e.g., as protectants, antiseptics, emollients, antipruritics, kerotolytics, and astringents. The vehicle or base of an ointment is of prime importance if the finished product is expected to function as any one of the above categories. In the case of a protective ointment, it serves to protect the skin against moisture, air, sun rays and other external factors. It is necessary that the ointment neither penetrates the human skin barriers nor facilitates the absorption of substances through this barrier. An antiseptic ointment is used to destroy or inhibit the growth of bacteria. Frequently bacterial infections are deeply seated; a base which has the capacity to either penetrate or dissolve and release the medication effectively is therefore desired. Ointments used for their emollient effect should be easy to apply, be non-greasy and effectively penetrate the skin.

There are five (5) classes or types of ointment bases which are differentiated on the basis of their physical composition. These are:

• oleaginous bases

• absorption bases

• water in oil emulsion bases

• oil in water emulsion bases

• water soluble or water miscible bases

Each ointment base type has different physical characteristics and therapeutic uses based upon the nature of its components. The following table summarizes the composition, properties, and common uses of each of the five types. For more information consult Remington's.

To incorporate an insoluble drug into these bases, pulverize the powder on the pill tile or with a mortar and pestle (above/right). Use a levigating agent to wet the powder and then incorporate the wetted powder into the ointment base. Generally, the amount of drug to be incorporated into the ointment will be much less than the amount of ointment. In other words, a small amount of drug will be

incorporated into a large amount of ointment. The process of geometric dilution will \"diluted\" the drug into the ointment. Geometric dilution involves a series of dilution steps. It begins by incorporating the drug into an amount of ointment of approximately the same size. Then a second amount of ointment approximately equal to the first mixture is added and mixed.This stepwise dilution process is continued all of the ointment has been used.

A good levigating agent is mineral oil since it is compatible with oleaginous bases. Sometimes using a small quantity of the base itself as the levigating agent is sufficient.

Soluble drugs can be incorporated into oleaginous bases by fusion. The base is liquefied over low heat (not to exceed 70°C) and then the drug is added to the

molten base. The mixture is then allowed to cool with occasional stirring.

Show how to incorporated a drug into an ointment using geometric dilution & 2 spatulas

Incorporating insoluble drugs into these bases can be done mechanically or by fusion. The final destination (internal or external phase of the emulsion) of the drug must be considered when selecting a levigating agent. If the drug will reside in the internal phase (water phase), then the levigating agent should be water soluble or miscible. Water, glycerin, alcohol, or propylene glycol would be suitable levigating agents. If the drug will reside in the external phase, then mineral oil should be used.

Water soluble ingredients can be added to the water phase of the w/o emulsion. If the drug will dissolve in a small amount of water, the aqueous solution can be added directly to the base using a pill tile and spatula. If a larger quantity of water is needed to solubilize the drug or if an aqueous solution is being added to the base, heat may be needed to compound the formulation. It may be necessary to add additional emulsifier to the emulsion to accommodate the added water. Some commercial emulsions do have the necessary excess emulsifier.

W/O Emulsion Bases Oils and insoluble powders can be directly incorporated into the external phase using a pill tile and spatula. If a levigating agent is to be used with the

insoluble powders, it should be miscible with the oil phase; mineral oil would be a suitable agent. Levigating agents may be needed with larger quantities of insoluble powders. If the insoluble powder has a different salt form that is oil soluble, consideration should be given to using that salt form.

The same comments that apply to incorporating water soluble ingredients into absorption bases also apply to w/o emulsion bases.

O/W Emulsion Bases

Water soluble powders can be directly incorporated into the external phase using a pill tile and spatula. If the powder is insoluble, the levigating agent should be water miscible so glycerin, propylene glycol, polyethylene glycol (PEG) 300 or 400, or alcohol would be acceptable. If the insoluble substance has a different salt form that is aqueous soluble, consideration should be given to using that salt form.

It may be more difficult to incorporate oil soluble ingredients into the o/w formulation. A small amount of oil can be incorporated into the base if there is excess emulsifier. Some commercial products do have the necessary excess emulsifier. If a larger portion of oil is to be added, the addition of more emulsifier may be necessary. If heat is used to incorporate the oil, it is important to work quickly so that water is not evaporated from the product. This will cause the product to become stiff and waxy.

Water Miscible Bases

Water soluble drugs can be dissolved in a small quantity of water and incorporated using a pill tile and spatula. Insoluble powders will require a water miscible levigating agent such as glycerin, propylene glycol, or polyethylene glycol 400. Oils can be added into these bases by first mixing the oil with glycerin or propylene glycol, and then incorporating the mixture into the base. Heat may be necessary if the quantity of liquid to add to the base is large.