Prevention Of Cap Locking Problem in Syrups by Additives And pH Adjustment Method

Syrups are concentrated solutions of sugar (such as sucrose) in water or other aqueous liquids with or without added flavoring agents and medicinal substances Sucrose. Sucrose is the most widely used sweetener, with a long history of use.  It is a white crystalline powder, soluble in water and alcohol.  It inhibits the growth of m.o. in solution at concentrations above 65wt% by reducing the water-activity coefficient. Official simple syrup is an 85% w/v solution of sucrose in water. During the preparation of sucrose solution, care should be taken to avoid charring and caramelization caused by heat. Sucrose is chemically and physically stable in the pH range of 4.0–8.0.  It is frequently used in conjunction with sorbitol, glycerin, and other polyols, which reduce its tendency to crystallize. Sugar syrups promote significant ‘‘cap-locking’’—the crystallization of the sugar on the cap and bottle thread, but the addition of glycerin (10–20%) minimizes this effect.  Glycerin is seldom used as a single sweetener in pharmaceuticals because it has a characteristic mouth warming and burning effect.

Chemical reaction: 2

Research works has been done on preventing crystallization of sucrose by treating with citric acid monohydrate and the Diphenhydramine hydrochloride syrup product manufactured by using sugar syrup where content of invert sugars is reduced to less than 15% w/w. (Heyam Ali etal) 4

MATERIALS

Sucrose purchased from the local market, Tagarapuvalasa, Visakhapatnam, Andhra Pradesh, India and the remaining chemicals were purchased from the Yarrow chemicals, Mumbai.

METHODOS

Syrups were prepared with additives and buffers according to the formula given in the tables 1,2 and Paracetamol syruos were prepared according to the formula given in the table3

Table1: Formulation Table for Syrups with Additives

Table2: Formulation Table F Invert Syrups with Buffers

Table3: Formulation of Paracetamol Syrups

Preparation of sugar syrup (66%w/w)⁵:

100 g of sugar syrup was prepared by heating 33.4 g of purified water to 70⁰C ±1⁰C in a syrup manufacturing vessel in a water bath. Then 66.6 g of sucrose was dissolved in the hot water in the manufacturing vessel with stirring. After that, the temperature was raised to 90⁰ ±1⁰ C. At this temp, the sucrose solution was heated for 45 minutes. Then sugar syrup was cooled to 40⁰ C. Finally weight of the sugar syrup was adjusted to 100 g with purified water and stirred for 2 minutes.Thus sugar syrup was prepared and considered as the control sample SS-1.

Preparation of partially inverted sugar syrup(66%w/w) with additives:

100 g of partially inverted sugar syrup was prepared by heating 33.3 g of purified water  to 70⁰C ±1⁰C in a syrup manufacturing vessel in a water bath. The additives in the required quantity ( as per the table  )was dissolved in hot purified water in a manufacturing container. Then 66.6 g of sucrose was dissolved in the hot water in manufacturing vessel in stirring. After that, the temperature was raised to 90⁰ ±1⁰ C. At this temp, the sucrose solution was heated for 45 minutes. Then the syrup(inverted) was cooled to 40⁰ C. Finallythe weight of the inverted sugar syrup was adjusted to 100g with purified water. Thus partially inverted sugar syrups were prepared.³All the inverted syrups were coded as per the table no

Preparation of partially inverted sugar syrup (66%w/w ) with buffers^6,7 :

100g of partially inverted sugar syrup with buffers mentioned above were prepared. First, 33.3g of purified water was heated to 70⁰ C ± 1⁰C in a syrup manufacturing vessel in a water bath. Then 66.6 g of sucrose was dissolved in the hot water in the manufacturing vessel with stirring. Then the sucrose solution was heated at 90⁰ ± 1⁰ C for 45 minutes. Afterwards, the sugar syrup was cooled at 40⁰ C. The final weight of the sugar syrup was adjusted to 100 g with buffers. The inverted syrups were observed visually for the crystal growth of sucrose for 6weeks and the results were given in the table Based on the results the Paracetamol syrups were prepared with citric acid mono hydrate, pH ,NaOH were prepared and evaluated for various parameters results were given in the table

Formulation of Paracetamol syrup with buffer PH-5^8-13:

PART-1:

First, 10g of PEG-6000 was heated at 50⁰ C. 2.5g of paracetamol was added to it, and the solution was stirred for 30 minutes. After that 2.5g of glycerin was heated at 50⁰ C and then added to the above solution (PEG-6000+paracetamol) under continuous stirring. The solution was stirred until the transparent solution was obtained. After that, the above mixture was added to the hot purified water under continuous stirring until the transparent solution was obtained.

Part-2:

Then 50g of partially inverted sugar syrup with pH-5 buffer-was prepared. First, 16.7 g of purified water was heated to 70⁰ C ± 1⁰C in a syrup manufacturing vessel in a water bath. Then 33.3 g of sucrose was dissolved in the hot water in the manufacturing vessel with stirring. Then the sucrose solution was heated at 90⁰ ± 1⁰ C for 45 minutes. Afterward, the sugar syrup was cooled at 40⁰ C. The final weight of the sugar syrup was adjusted to 50 g with buffer PH-5.Slowly add part 1 to part 2 under continuous stirring. And it was labelled as IP-PP2.

Visual inspection of crystal growth on petridishes , Bottle necks and caps

The crystal growth was observed in syrups by pouring in petridishes and caps initially and after 6 week duration. The results were shown in the figures  Based on the results the crystal growth was observed in simple syrup ,Syrups made with Citric acid and pH 6 buffer. There was no crystal growth in syrups made with citric acid monohydrate, NaOH and pH  5 buffer and these additives were chosen to prepare paracetamol syrups. After 6 weeks the paracetamol syrup(P-SS) has shown crystal growth in petridish and on bottle cap. The paracetamol syrup made with buffers(pH 6) and NaOH  has not shown any crystal growth.

       
           
       
           
           
       
Fig2: Syrups in petridisehes initial                          Fig3: Bottle caps initial

       
           
       
       
           
       
 Fig6: Paracetamol syrups in petridishes(initial)     Fig7:Paracetamol syrup on bottle neck after 6 weeks

Evaluation¹⁴:

Biochemical tests: These tests were performed to identify the presence of sugars. following tests are performed

Benedict's test:

Mix equal volumes of Benidict’s reagent and test solution in test solution in a test tube. Heat in boiling water bath for 5 mins. the solution appears green yellow or red colour depending on the amount of reducing sugar present in the test solution.

The samples were passed and the results were given in the Table6.

Surface Tension:

The surface tension of the prepared syrups was measured using a stalagmometer and a specific gravity bottle. Results were given in Table6.

Specific Gravity:

The specific gravity of the prepared syrups was measured using the specific gravity bottle. Results are given in table6.

Viscosity:

The viscosity of the syrups was measured using Ostwald’s viscometer and calculated by using the formula given below. Results are given in the table6.

pH:

pH Measurement using a pH Meter:

The pH of the prepared syrups was measured using a pH meter.

Results are given in the table6.

Measurement of optical activity with Polarimeter¹⁴

After ensuring the equipment tube was clean, The instrument set up on the bench with the analyzer head facing the operator, an illuminated sodium lamp is attached with equipment through a bracket. The redindicator  glowed  on the transformer and then waited for 5 minutes for complete illumination of sodium vapor lamp. The position of the Sodium vapor lamp is such that the field can be seen clearly while viewing through the lower eyepiece. The lower eyepiece adjusted properly either towards or away from the eye to view clearly. After focusing on the upper eyepiece the scale graduation and  a vertical line called the reference line were viewed. The sample was filled in the tube and placed in the polarimeter and viewed  through the lower eyepiece and until match the colour shade to be similar in both sections by rotating the knob placed on the opposite to the eyepiece. Then the scale reading was measured and substituted in the equation to know the specific rotation value. The results were given in the table8.

Determination of Reducing Sugars by the Modified Ofner Titrimetric method^15-20:

The complex formed between Cu+ ions and potassium sodium tartrate is reduced by reducing sugars to univalent Cu+ which is precipitated as CU20. The precipitated CU20 is then determined by iodometric titration. The CU20 is oxidized by an excess is back titrated with sodntm thiosulphate. The reaction between the reducing sugars and the Cu++ complex is not stoichiometric. The amount of CUZO formed depends upon the prescribed reaction conditions which therefore must be strictly followed. It has been determined that 1 ml of 0.016 15 mol/1 iodine solution is equivalent to 1mg of reducing sugars, once the correction for the reducing effect of sucrose has been taken into account.

Hot value:

After preparation of Ofners solution 50ml of the ofners solution was mixed with 50 ml of each syrup (Simple syrup,) separately ,some pumice pieces were added and boiled for 5minutes cooled for 10minutes after cooling 1ml concentrated acetic acid and iodine solutions were added until the solution turns blue colour. the excess iodine  was back titrated with 10 to 15 ml sodium thiosulfate. 15ml 1M HCl added and titrated against 0.0333mol/l,1ml of starch was added before the endpoint reached.

Cold value:

50 ml of each syrup was mixed with 50ml of Ofners solution and the procedure given in hot value was repeated without heating and volume of iodine and sodium thiosulfate was noted.

Blank value:

50ml of water was added to 50ml of ofners solution and the procedure in hot valuw was repeated with out heating and volumes of iodine and sodium thio sulfate were noted.

Expression of Results : the terms involved in calculation was explained in the table no1 and results were given in table 4.

Corrected consumption of 0.01667 mol/1 iodine solution:

Calculated hot value,A = (V₁ x f₁) – (V₂x f_Th)

Calculated cold value, B = (V₃x f₁) - (V₄ x f_th)

Calculated blank value,C = (V5X f₁) - (Vx f_th)

Invert sugar, mg/lcg = (A- B- C- D) X1OOO s

where s = the amount of sample in 50 ml of prepared solution based on the calculation the amount of inverted sugar in all the syrups was measured and the results were given in the table7.

RESULTS AND DISCUSSION

Table5: Results Of Bendicts Test

The results from Bendicts test were given in the table 5 and these results indicated that all the syrups have reducing sugars except simple syrup.

The viscosity, Surface tension, pH and specific gravity value of all the prepared syrups wer given in the table all the results meet the required specifications.

Ofner’s Method Calculation:

Table7:  Results From Ofners Calculation