Effervescent Tablet : Developing and Method of Manufacturing

Effervecent tablets made by some method, that is by wet granulation, dry granulation, and the method of fluidization. Fluidization method wurster method, using a special spray equipment complete with channels spray binder and air duct heating.

Effervescent Tablet requires require special conditions and methods for its production because there are two ingredients that can not be united which is salt sodium bicarbonate and organic acid as a producer of carbon dioxide. The second reaction, this material will be accelerated by the presence of water, therefore Effervescent tablet during its journey from the end of production into the hands of patients should not be the slightest contact with water. In addition, high temperatures can also accelerate the

Effervescent tablet-making process requires special conditions, humidity should be relatively low and the temperature must be cold to prevent the granules or tablets attached to the machine because of the effect of moisture from the air.

Problems On Some Active Compounds in Formulating Tablet

• Papaverine HCl,
if used water in formulating, this drug will dissolve, then use solvents that do not dissolve the active ingredient

•Hydrophobic substance (phenylbutazone, Vioform, Paracetamol, and chloramphenicol esther)
In formulatin g hydrophobic substances, you can add Tween 80 0.01% or saponin 5% of weight of the tablet (add mucilago amyli as much as 0.03%)

• Diazepam
if made granule, Diazepam will become rough granules, therefore, should be smoothed first.

•Vitamin C and Paracetamol
In preparing combination of vitamin C and paracetamol, you should use a non-water solvent, and dry with a dehumidifier.

Vitamin C Effervescent Tablet : Formula, Manufacturing and Consideration of Material and Method of Manufacture Selection

One effervescent tablet made with weights 1.5 grams (1500 mg).
Formula for 1 piece of Vitamin C effervescent tablets:

  • Vitamin C 500 mg
  • Pyridoxine 20 mg
  • PVP 3% 45 mg
  • Sucrose 15% 225 mg
  • Citric Acid Monohydrate 208 mg
  • Tartaric Acid 222,9 mg
  • Sodium Bicarbonate 249,5 mg
  • PEG 8000 30 mg 
Read more about :Effervescent Tablet Formulation and Manufacture

Microencapsulation of Rifampicin Using Combination of Sodium Alginate and Carbopol as Coat Materials



Carbopol 974P is a synthetic high molecular weight cross-linked polymer of acrylic acid. It is a safe and nontoxic. It is an excellent thickening, emulsifying, suspending and gelling agent. Because of its control release and gel formation properties, Carbopol 974P was chosen as the encapsulation polymer.

Appearance : Fluffy, white, mildly acidic polymer
Bulk Density : Approximately 208 kg/m3 (13 lbs.ft3)
Specific gravity : 1.41
Moisture content : 2.0% maximum
Equilibrium moisture content : 8-10% (at 50% relative humidity)
PKa : 6.0 ± 0.5
pH of 1.0% water dispersion : 2.5 - 3.0
pH of 0.5% water dispersion : 2.7 - 3.5
Equivalent weight : 76 ± 4
Ash content : 0.009 ppm (average)
Glass transition temperature : 100-105C (212-221F)

Microencapsulation of Rifampicin Using Combination of Cellulose Acetate Phthalate and Polyethylene Glycol as Coat Materials

  • Cellulose Acetate Phthalate 64 g
  • Rifampicin 800 g
  • Polyethylene Glycol 4000 6.4 g
  • Water 1200 ml
  • Hydrochloric Acid 0.5 ml
  • Dichloromethane 200 ml
  • Isopropyl Alcohol 100 ml

  1. Dissolve Cellulose Acetate Phthalate and Polyethylene Glycol 4000 in Isopropyl Alcohol & Dichloromethane mixture
  2. Disperse rifampicin in water containing 0.5 ml of Hydrochloric Acid to make a slurry and keep on a water bath at50° C.
  3. Add Cellulose Acetate Phthalate solution to the slurry with constant stirring.
  4. Filter off the microcapsules and dry them.

The above mentioned microcapsules of Rifampicin may be blended with other anti-tubercular drugs and suitable excipients to formulate into tablets, capsules or suspension.

Special Problem in Compressing Tablet Process

1. Sticky on Die

  • Inherent in the die and difficult to remove
  • Loud noise in engine
  • Tablet brittle, ugly, rough side of the tablet, sometimes black

  • Antidherent less
  • lack of or improper lubricant
  • Example: Tablet aspirin sticky with Magnesium stearate, stearic acid should be used (which micronize because the function of lubricant between the particles are so fine that will be covered by the lubricant).
  • Water content is high will cause the attachment or sticky on the die, while low water levels can cause the laminating or capping.
  • The possibility of chemical or physical interaction, example :physical interaction between etoxy benzamin with caffeine, glyceryl guaiacolate with promethazine HCl, which are melting so high adhesives and eventually become sticky.
  • Raw materials with very low melting point. Example: Ibuprofen, glyceryl guaiacolate, Ciprofloxacin (antibiotic imidazole derivatives).

Settlement Issues/Problem Solution:
  • Improve antiadherent and lubricants
  • Replacement of a suitable lubricant
  • Reduce the number of coarse granules
  • Reduce the amount of water but do not get under the optimum, because the tablet becomes less good. If you already know the amount of wetting agent, carried out by adding the wetting agent to a binder solution, ie materials that do not evaporate but wet, for example : Propylene glycol or glycerin.
  • If there is sticky because of the punch and die may be damaged, because if defects in the punch, it will be attached so that the smooth punch and die.
  • If possible compressing at low temperature and low humidity due specifically to the active ingredient with a low melting point or eutectic mixture occurs, the eutectic mixture of substances more easily absorb water. Example: The combination of ampicillin with Clavulanic acid, where clavulanic acid easily destroyed by high humidity and temperature. Therefore, the manufacturing is done in a low temperature and RH.
  • Change of filler, filler material with high melting point and can adsorbing, such as SiO2 and Aerosil (adsorbent). Aerosil Addition in tablet tablets will cause the appearance of good, clear and shiny, but the longer the disintegration time.

Problems In Preparation Tablets

Problems that may arise is with regard to how to make good preparations and in accordance with their intended use.

To make good preparations needed pre-formulation data covering stability, organoleptic, physicochemical properties, and other data that can be expected to support the raw materials that are suitable for the formation of a preparation is good and the achievement of the intended use.

As for the problems that may occur:

1. Incompatible active substance (melting, change color, decompose, and so on).

Rifampicin and Isoniazid Fixed Dose Combination Tablet (Rifampicin-Isoniazid FDC Tablet) Pre-Formulation

Fixed dose combination (FDC) formulations became popular in the treatment of tuberculosis (TB) because of the better patient compliance, reduced risk of monotherapy and emergence of drug resistance in contrast to treatment with separate formulations of two to four first-line drugs.
It has been reported that the poor absorption of rifampicin from combination products may be due to decomposition of the drug in acidic stomach conditions, which is accelerated in the presence of isoniazid The mechanism of this degradation was proposed by Singh et al.

Problems in Formulating TBC Drug FDC (Rifampicin and Isonazid Tablet)

Studies revealed that the decomposition of rifampicin in acidic conditions in the absence of isoniazid stopped at the formation of 3-formylrifamycin, while the reaction in the presence of isoniazid proceeded to form a hydrazone between 3-formylrifamycin and isoniazid. Further, it was suggested that once 3-formylrifamycin is formed, it interacts with isoniazid to form the hydrazone, through a fast second order reaction. As hydrazone are unstable in acid conditions, 3-formylrifamycin and isoniazid are regenerated in areversible manner through a slower first order reaction. In this complex reaction process, rifampicin is further degraded, while isoniazid is recovered.

Combination products of rifampicin and isoniazid form isonicotinyl hydrazone (HYD) as a result of the interaction of the imine group of rifampicin and the amino group of isoniazid. While this reaction is slow in a solid state, it increases exponentially in the presence of acid and other tubercular drugs, such as ethambutol hydrochloride and pyrazinamide. The interaction between rifampicin and isoniazid came to light after a pharmacokinetic study of rifampicin in combination products the gastric acid led to a significant degradation of rifampicin, resulting in a 32% reduction in bioavailability Preformulation studies and a forced degradation study can detect such interactions much earlier.

Tablet Weight Variation: What Causes It and How to Deal Weight Variations

In the process of compressing a tablet, of course there are problems, one of them is the weight variation. Usually, the range is still tolerable for large-sized tablets (diameter> 10 mm) was 3%, while for small tablet (diameter <7mm) is 5%. However, this specification ranges vary depending on the respective industry and the active ingredient of the drug. If the active ingredient is an extremely potent drug, in terms of the number of doses are very small (microgram scale) has a large effect, then the range specifications for tablet weight variation would be minimized.

Tablet weight variation in compressing process is not a trivial thing. Moreover, when affecting the uniformity of dosage units.

Tablet weight variation may be caused by:
  • Distribution at Hoover caused the vibration. So, small granule pushed, large granules will come out first, because there is a process of consolidation. Therefore, needs to be put a uniform granule size. So, before the compressing process begins, better evaluation the particle size distribution first.
  • The flow of granules is not good / not free-flowing granules
  • particle distribution is not normal, because the specific gravity is different, so that the flow is bad.
  • Keep the uniform of particle size distribution. Not too many fines and not too many granules. Granules with a large particle diameter which causes the resultant tablet has a variety of unsightly weight, while too fine granules which causes unsightly flow time.
  • lubricant or glidant less or not mixed evenly. 

Special Problems That Exist When Formulating Some Tablets

1. Eutectic Mixture
Weigh both the active substance in proportion, put in a mortar and crushed. If it’s melting means eutectic.
Another way is, after both active ingredient mixed, add starch (musilago) with water, if it’s not dry not, mean eutectic, or you can replace starch with PVP alcohol.

2. Ethambutol Tablet Preparation and Formulation
Must be coat with the coating solution that alcohol-soluble and fatty acids soluble but not water soluble, preferably coated with Cetosel. Ethambutol if granulated with PVP / alcohol will be more cake. So, direct compression or dry granulation / slugging more prefer ble. With slugging, compactness will go down, but friability will be up. The technique of PVP addition : add PVP first into the mass then add alcohol until homogenous, so, the total amount is right.

3. Vitamin C
Do not use Avicel, this speed up the oxidation of vitamin C. Can be used in PVP, but the result is not good. Put starch in the vacuum or could also be used Cetosel in alcohol / eksplotab / starch. Do not use with wet granulation because of the disintegration time would be bad.

Avicel is a good use if not compatible with the active substance. Avicel could be used in direct compression, or wet granulation as a filler. If Avicel not water soluble, it can act as in the outer phase and inner phase.
If Avicel used in external phase, dry starch should be removed. So, the composition of outer phase is:

R /
Avicel 6%
Talk 1% (net)
Mg stearate 1%

Likewise, if used Aerosil in outer phase, talk was reduce because it has functioned well as glidant.

4. Starch
Starch is a good amount of 30%. If the amount is high, added substance Starch 1500 30%, then weight of the tablet will be even greater, while that have to be added is a lubricant, glidant, then starch added should be less than 30% which makes the flow to be poor. To overcome this, use Avicel which can act as a filler also disintegrant.
The combination of Starch 1500 and Eksplotab is good for the manufacture of tablets by direct compression as a disintegrant, should not be used as filler.

5. Dry Granulation Manufacturing
ARC 591 do not use alcohol-containing water (use alcohol that is not watery). If containingwater, it can be difficult to reconstituted.

6. Use of Pharmacot, Etocel, PVP
Only for active substances that must not hit the water (because it will decompose). The combination of starch 1500 and Avicel only for directcompression, the amount of Avicel should be reduced and the amount of Starch is 30%. Starch 1500 is not allowed to wet granulation with starch as a filler because the water will form a gel that can serve as a strong binder. But, as the crusher to SL can be used with wet granulation technique.

7. Extracts for Tablet
Condensed extract was dissolved in 70% ethanol and then dried with SL (Saccharum Lactis). For Belladona extract the composition is 1:3.

Pre-Formulation, Formulation and Manufacturing of Aspirin Chewable Tablet for Children

Acetylsalicylic Acid, also known by trade name Aspirin, is an acetyl derivative of salicylic acid that is a white, crystalline, weakly acidic substance, with melting point 137°C. It is useful in the relief of headache and muscle and joint aches. Aspirin is also effective in reducing fever, inflammation, and swelling and thus has been used for treatment of rheumatoid arthritis, rheumatic fever, and mild infection. Large doses cause acid-base imbalance and respiratory disturbances and can be fatal, especially in children. Acetaminophen (known by trade name Tylenol), which does not cause gastric irritation but does lower fever and relieve pain, is often substituted for Aspirin.

Chewing chewable tablets of aspirin produces the most rapid and biggest absorption compared to swallowing solid tablets or chewing and then swallowing solid tablets.

Formulation of Aspirin Chewable Tablet

Aspirin Chewable Tablet per Tablet
AlOH (Dried gel)          6.5 %       13 mg
Aspirin                          40.5%      81 mg
Talc                              1%            2 mg
Primogel                        4%            8 mg
NuTab                           46.7%     93.4 mg
Mafco Magna Sweet      0.3%       0.6 mg
Orange Flavor                1 %          2 mg

ANTI-MOSQUITO LOTION : Formula, Preparation and Evaluation

According to WHO, Indonesia is a country of endemic dengue fever mosquito. Approximately 2-5% of the world population is in danger of dengue fever disease. It is necessary to make an action for this outbreak is not widespread, and one way is by controlling disease vectors and self protection.

Lots of synthetic insecticides that can cause side effects and resistance, make people switch to products derived from natural materials. One is a plant that can be used is lemongrass (Cymbopogon nardus), which has a volatile oil content of which geraniol, methyl heptenon, and especially is citronellal. Content of these are toxic and can cause death due to fluid loss mosquito constantly so it will lack body fluids.

Some dosage forms have been tried to create a formula anti mosquito, one of the most popular dosage form lotions. This is due to ease of use and practical. Lotion is an emulsion, so we need a proper surfactant. Some things to consider in making preparations lotion is stability. Lotion would be damaged if disturbed system alloys mainly due to changes in temperature and composition are not sesai with prescribed dose.


Part A:
R / Stearic acid 10.68 g
Olive oil 15 ml
Cera alba 1.98 g
Nipagin 0.18 g
Lemongrass essential oil 1 ml

Part B:
R / triethanolamine 5.34 ml
Distilled water 112.11 ml


Gardenia blue has been found stable at pH 3.5 and water solubility 7. Pikosianin does not dissolve in acid solubility (pH 3) and denatured at temperatures above 450C at pH 5 and 7. Which leads to discoloration. Exposed to visible light from 3x105 lux for 24 hours in water solubility at pH 5 and 7 caused 80% degraded.

To top of gardenia blue absorption is not dependent on pH (at pH 3, 5 and 7), with a maximum wavelength (╬╗maks) 596 nm. But its maximum absorption is determined by the amino acids used to form the blue color of the gardenia, in the range of wavelengths between 580 nm to 597 nm

The spectrum of pikosianin influenced by pH and maximum wavelength at 616 nm and 620 nm, especially for pH 5 and 7. Variations of pikosianin ╬╗maks value depends on the pH and the ratio 620 nm/280 nm for states that pikosianin is an unstable compound and composition variations may depend on sources, production methods and materials - material enhancements.

Stability of Natural Dyes on Light Blue : Gardenia blue, Phycocyanin, and Indigo

Three blue (Gardenia blue, phycocyanin, and indigo) has a maximum wavelength of 313 nm and 600 nm.

A. Blue Gardenia
Gardenia blue has been found stable at temperatures up to 800C in water solubility pH 3.5 and 7. When exposed to visible light from 3x105 lux for 24 hours resulted in approximately 50% degraded in water solubility.

Number of gardenia degraded by light with high intensity will depend on the number of amino acids used to prepare the blue color of the gardenia. In general, blue gardenia can remain stable even if exposed to light exposure is lower than like the ones in supermarkets (approximately 1500 Lux).

B. Phycocianin
Phycocianin known to be unstable on heating and lighting in the water solubility. When exposed to visible light from 3x105 lux for 24 hours in water solubility at pH 5 and 7 caused 80% portion degraded.


Consumer attention to the security dye synthesis increased use of natural dyes. Blue dye can be used in the long term, lead to an increased use of natural blue color, especially in food and beverage industry. Use food coloring to note the stability in the knowledge of degradation processes, the optimization of production, packaging and storage. Such as to heat and light of a natural dye that is blue and gardenia blue, and indigo pycocianin recently conducted a study to staining solutions

Description Plants Producing Blue Natural Dyes

1. Indigo
Division: Magnoliophyta
Class: Magnoliopsida
Nation: Fabales
Tribe: Fabaceae
Genus: Indigofera
Type: Indigofera tinctoria

Tarum (from Sundanese), tilapia, or indigo (Indigofera, tribal legumes or Fabaceae) is a plant producing a natural blue color. Marga Indigofera (indigo plant), large (approximately 700 species) spread throughout the tropical and subtropical regions of Asia, Africa and America most of the species growing in southern Africa and the Himalayas. Indigofera plants containing glucoside indikan. Indigo blue color is obtained from soaking the leaves (in quantity). The blue color produced by soaking the leaves during the night. After overnight will form a layer on top of the green or blue. This liquid is then boiled, then dried in the sun to dry. As the dye-producing plants, Indigofera planted in the highlands and as a secondary crop paddy land. Land should berdainase pretty good. If used as cover crops, Indigofera only be planted in the garden with little shade or without shade. This species enjoys a hot and humid climate with rainfall of not less than 1,750 mm / year. This plant is able to survive against pengenangan for 2 months. Indigo precursors in plants is indoksil, resulting glucoside indican, isatin esters B, where after both extraction and chemical modification of the complex of indigo dye.

Read More : Stability of Natural Dyes on Light Blue : Gardenia blue, Phycocyanin, and Indigo