Description of the Prlor Art Antipyretics, antibiotics and vitamins have been conventionally formulated in the forms of tablet, capsule, liquid, injection solution and syrup. The conventional dosage forms are, however, proven to be less satisfactory in the sense that they are not convenient for administering to children. Accordingly, particular attention should be paid in choosing the dosage forms, especially, orally administrable pharmaceutical formulations are selected under a careful consideration of taste and mouth feel in oral cavity.

Unfortunately, many medicines and active ingredients are bitter in taste or else hold uncomfortable taste, rough or chalky feeling. With the recent development in pharmaceutical technology, to improve taste and/or mouth feel in oral cavity, the pharmaceutical formulations of relatively easy administration for children such as chewable tablet, jelly-like tablet, granules, etc., have been developed. They are commercially available though these pharmaceutical formulations are not ideal in terms of children's affinity. Under the circumstances, there are strong reasons for exploring and developing new type of pharmaceutical formulation for children.

SUMMARY OF THE INVENTION The present inventors have made efforts to develop an icecream-type pharmaceutical formulation which can be applied in drugs such as antipyretics, antibiotics and vitamins, and found that it provides excellent drug absorption with improved patient's drug compliance in light of easy oral application and high affinity.

The primary object of the present invention is, therefore, to provide an icecream-type pharmaceutical formulation.

The other object of the invention is to provide a process for preparing the icecream-type pharmaceutical formulation.

Another object of the invention is to provide icecream-type formulations of antipyretic, antibiotic and vitamin.

BRIEF DESCRIPTION OF THE DRAWINGS The above and the other objects and features of the present invention will become apparent from the following descriptions given in conjunction with the accompanying drawings, in which: Figure 1 is a high performance liquid chromatography chromatogram of acetaminophen in blood.

Figure 2 is a graph showing blood level of tablet- type and icecream-type acetaminophen after oral administration.

DETAILED DESCRIPTION OF THE INVENTION Icecream-type pharmaceutical formulation of the present invention is prepared by the steps of: mixing egg

yolk and milk with stirring until they are completely mixed; whipping cream until it is reduced to pulp and mixing it with the said mixture in a volume ratio of 9: 1 to 5: 5, more preferably 8: 2 to 6: 4, most preferably 7: 3; adding drugs into the said mixture in a ratio of 0.1 to 20wt% and blending them; and, finally putting them into an icecream maker and formulating into a pharmaceutical formula by subjecting at the temperature range of 0°C to -10°C.

In the preparation of the icecream-type formulation, sugar and/or cocoa may be-further added to the mixture of egg yolk and milk according to the patient's preference, and coconut hard fat may substitute for the egg yolk.

Further, the milk includes soy bean milk, processed skim milk (containing 7.2% skimmed milk powder) and plain milk.

And, hue cream includes: commercially available emulsion cream which can be obtained by the centrifuge of animal/vegetable oil; and, carboxymethylcellulose (CMC) solution. Though several pharmaceutical formulations of antipyretics, antibiotics or vitamins are illustrated in the Examples below, they do not specifically limit the drugs contained in the formulation. The antipyretics include acetaminophen, aspirin, ibuprofen, ketoprofen and isopropyl-antipyrin, preferably acetaminophen and/or mixture thereofs, the antibiotics include amoxicillin, ampic-llin, erythromycin, lincomycin, and cefalexin, most preferably amoxicillin, and the vitamins include retinol acetate, cholecalciferol, tocopherol acetate, ascorbic acid, thiamine nitrate, riboflamin, pyridoxine hydrochloride, nicotinamide and cyanocobalamin.

The present invention is further illustrated in the following examples, which should not be taken to limit the scope of the invention.

Example 1 : Preparation of icecream-type formulation containing an antipyretic of acetaminophen

Example 1-1 Sugar, cocoa, egg yolk and milk were weighed in the ratios shown in Table 1 below, and mixed with stirring until they were completely dissolved. Then, commercially available emulsion cream was whipped until it was reduced to pulp and mixed with the said mixture. And then, acetaminophen, an antipyretic, was added to the mixture, blended, and put in an icecream maker (Philips, HR2034) and subjected at a temperature of 0 C to-10 C, to give an icecream-type formula.

Table 1. The contents of icecream-type formulation containing acetaminophen Ingredients Ratio (wt%) Milk q. s. 100.00 Sugar 18.00 Cocoa 3.60 Egg yolk 6.00 Emulsion cream30. 00 Acetaminophen 0. 20 Example1-2 An icecream-type antipyretic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 2 below.

Table 2. The contents of icecream-type formulation containing acetaminophen Ingredients Ratio (wt%) Milk q. s. 100.00 Sugar 18.00 Cocoa 3.60 Egg yolk 6.00 Emulsioncream 30.00 Acetaminophen 1. 00

Example 1-3 An icecream-type antipyretic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 3 below.

Table 3. The contents of icecream-type formulation containing acetaminophen Ingredients-Ratio (wt%) Milk q. s. 100.00 Sugar 18.00 Cocoa 3.60 Egg yolk 6.00 Emulsion cream 30.00 Acetaminophen 10. 00

Example 2: Preparation of icecream-type formulation containing an antibiotic of amoxicillin Example 2-1 An icecream-type antibiotic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 4 below.

Table 4: The contents of icecream-type formulation containing amoxicillin

Ingredients Ratio (wt%) Milk a. s. 100.00 Sugar 18. Cocoa3.60 Egg 6.00 Emulsioncream 30.00 Amoxicillin 0. 20

Example 2-2 An icecream-type antibiotic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 5 below.

Table 5: The contents of icecream-type formulation containing amoxicillin IngredientsRatio (wt%) Milk 100.00 Sugar 18. 00 Cocoa j 3.60 Eggyolk6.00 Emulsion cream30.00 Amoxicillin1.00

Example 2-3 An icecream-type antibiotic formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients shown in Table 6 below.

Table 6: The contents of icecream-type formulation containing amoxicillin (wt%)IngredientsRatio Milk q. s. 100.00 Sugar | 18.00 Cocoa 3.60 Egg yolk 6.00 Emulsion cream30.00 Amoxicillin10. 00

Example 3: Preparation of icecream-type formulation containing vitamins

Example 3-1: An icecream-type multi-vitamin formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients of retinol acetate, cholecalciferol, tocopherol acetate, ascorbic acid, thiamine nitrate, riboflavin, pyridoxine hydrochloride, nicotinamide and cyanocobalamin as shown in Table 7 below.

Table 7: The contents of icecream-type formulation containing vitamines Ingredients Ratio (wt%) # Milk q. s. 100.00 Sugar18.00 Cocoa 3. 60 Egg 6.00 30.00Emulsioncream 0.002Retinolacetate Cholecalciferol 0.0004 Tocopherol acetate 0.02 0.04Ascorbicacid 0.0008Thiaminenitrate Riboflavin I 0.0008 0.0012Pyridoxinehydrochloride Nicotinamide0.008 Cyanocobalamin0.000004 Example 3-2: An icecream-type multi-vitamin formulation was prepared in an analogous manner as in Example 1-1, except for employing the ingredients of retinol acetate, cholecalciferol, tocopherol acetate, ascorbic acid, <BR> <BR> thiamine nitrate, riboflavin, pyridoxine hydrochloride, nicotinamide and cyanocobalamin as shown in Table 8 below. Table 8: The contents of icecream-type formulation containingviyamins (wt%)IngredientsRatio 100.00Milkq.s. Sugar 18.00 Cocoa3.60 Egg6.00 30.00Emulsioncream 0.1Retinolacetate Cholecalciferol0.02 1.0Tocopherolacetate Ascorbic acid'2. 0 Thiamine nitrate0.04 Riboflavin0.04 0.06Pyridoxinehydrochloride Nicotinamide 0.4 Cyanocobalamin 0.0002

Example 4: Measurement of Blood Level of Drugs To measure the blood level of acetaminophen, male SD rats were cannulized in arteriae femoralis after the ether treatment. When the rats were come out of the e her, commercially available acetaminophen tablet and icecream- type formulation were orally administered with an eaual amount of 100mg/kgBW as acetaminophen per each. Blood was collecte in an equal interval and injected to high performance liquid chromatography (HPLC) working under the analvsis condition below. The HPLC chromatogra of acetaminophen in blood is shown in Figure 1.

Condition for HPLC Analvsis: Column: u Bonaapak C18 (Maters, U. S. A.) Mobile phase: acetonitrile : 1% acetate (1: 9, v: v) -1ml/minflowrate Detector: UV spectrophotometer (#=254nm)

Example 5: Changes in Blood Level of Acetaminophen Changes in blood level of acetaminophen were monitored by the method illustrated in Example 4, after oral administration of 50g icecream-type formulation prepared in Example 2-2 (containing 500mg acetaminophen) and commercially available acetaminophen tablet (containing 500mg acetaminophen) in an amount of 100mg/kg to experimental rats (see: Figure 2). As shown in Figure 2, Cl} for the icecream-type formulation containing acetaminophen (o) was showno at 20min while tablet form (*) was at 30min, and the blood level of drug in the icecream- type formulation was 3 times as high as the tablet-type formulation.

Example 6: Changes in Blood Level of Amoxicillin Changes in blood level of amoxicillin were monitored by the method illustrated in Example 4, after oral administration of 50g icecream-type formulation prepared in Example 2-2 (containing 500mg amoxicillin) and commercially available amoxicillin capsule (containing 500mg amoxicillin) in an amount of 10mg/kg to experimental rats.

As a result, it was clearly determined that both of the icecream-type formulation and capsule-type formulation of amoxicillin showed similar blood level curve.

Example 7: Changes in Blood Level of Tocopherol Acetate Changes in blood level of tocopherol acetate were monitored by the method illustrated in Example 4, after oral administration of 50g icecream-type formulation prepared in Example 3-2 (containing 500mg tocopherol acetate) and commercially available tocopherol acetate tablet (containing 500mg tocopherol acetate) in an amount of lmg/kg to experimental rats.

As a result, both of the icecream-type formulation and tablet-type formulation of tocopherol acetate showed similar blood level curve.

Acute Toxicity Acute toxicities of icecream-type formulations of antipyretics, antibiotics, and vitamins prepared in Examples 1,2 and 3 were investigated by employing 5 sets of male and female rats, which revealed that no mortal rat was detected up to the level of 5g/kg/day which is 500 times of antipyretics, 5000 times of antibiotics and 50000 times of vitamins in terms of their effective amounts.

The icecream-type formulation of present invention which comprises antipyretic, antibiotic, or vitamin as an active ingredient is formulated for orally applicable purpose, in accordance with the conventional formulating method by containing surfactants, excipients, tinctorials, stabilizers, buffers, suspensions, isotonic solution, and other additives, organic or inorganic carriers.

The icecream-type formulation may be administered to children in an oral dosage in an amount of 2 to 20mg/kg (20kg as a standard weight), while it may be varied depending on the type of drugs, medical treatments, diseases, patient's age and duration of medication.

As clearly illustrated and demonstrated as above, the present invention provides an icecream-type pharmaceutical formulation and a process for preparing the same.

Icecream-type pharmaceutical formulations prepared by the invention have higher drug compliance to children with easy administration and good absorption and thus may substitute for troches.

Although the preferred embodiments of the present invention have been disclosed for illustrative purpose, those who are skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.