Soft gelatin capsules

Properties1- they are made of gelatin glycerin (plasticizers)2- they are thicker than hard gelatin capsule3- they contain 6-13% water similar to hard gelatin capsules4- the hardness of the soft gelatin capsule is controlled by the ratio between plasticizer & dry gelatin5- they may contain, dyes, opaquing agents, preservatives, flavoring agents & sweetening agents

Applications of soft gelatin capsules

1- drugs in solutions or suspensions are incorporated as well as dry powders2- very useful in formulation of volatile air-sensitive drugs3- pastes ointments also may be packed into soft gels

Advantages of filling liquid drugs over dry drugs

1- greater content uniformity because the liquid dose is more accurately measured2- the greater dissolution of the drug because a drug is already in the solution or suspension forms

Disadvantages

1- volatile compounds such as alcohols, esters, low m wt water-soluble materials can not be formulated as soft gels2- liquid-filled capsules may increase the chance of undesired interaction between the drug the shell

Enteric coated capsules (delayed release capsules) capsules that are coated to resist the releasing of the drug in the gastric secretions of the stomach release it in the intestine why?

1- To avoid gastric disorders such as nausea & irritatione.g: NSAD's, Aminophylline iron salts2- To avoid drug degradatione.g: Erythromycin: acid hydrolyzedpolypeptides: enzymatically hydrolyzedtestosterone: enzymatically metabolized3- To obtain delayed, controlled or S.Re.g: Theophylline & barbiturates4- To exert local actione.g: Intestinal antiseptics & anthelmintic5- To prevent drugs from being interfered with food digestione.g: Tannins, salts of heavy metals

Capsules can be made enteric by

1- the sealed capsules are dipped in the polymeric solution and then dried2- such enteric-coated capsules will resist bursting in gastric secretions for 5 hrs While they will disintegrate in the pancreatic solutions within 2 hsVerification test:pepsin + HCl + waterPancreatin + NaCo3 + water

1- Synthetic polymers

Enteric coatings are prepared from materials that have groups which are insoluble at low pH but dissolve in higher pH such as1- cellulose acetate phthalate2- ammoniated shellac

Mechanisms of removing an enteric coatings

1- ionization2- Length of contact time with moisture3- Hydrolysis and or/ emulsification

1- ionization

1- synthetic polymer which will be in unionized form (insoluble form) at low pH of the stomach2- by increasing pH along the GIT, the polymer is ionized to the soluble form3- the coating is then dissolved followed by drug release

2- Length of contact time with moisture

1- the removal of the enteric coating depends on the contact time with the moisture of the surrounding2- The contact time consequently depends on the thickness of the coating

3- Hydrolysis and or/ emulsification

In this mechanism, enteric coating is either1- Hydrolyzed----- intestinal enzymes2- Emulsified ----- dispersed bile saltsexamples of coatings which are removed by those mechanisms: ethylcellulose - fatty derivatives - ester butyl stearate

Determination of dosage unit uniformity by

1- weight variation2- Content uniformity

weight variation

1- Hard capsules2- Soft gelatin capsules

1- Hard capsules

1- weight 10 intact capsules individually to obtain (w1)2- remove the contents of each capsule3- weight the empty shells individually (w2)4- calculate the net weight for each capsule content by subtracting w1 - w25- calculate the amount of the active ingredient in each capsule

2- Soft gelatin capsules

1- weight 10 intact capsules individually to obtain (w1)2- cut to open the capsule with sharp blade3- remove the contents by washing with suitable solvent4- allow the solvent to evaporate at room temperature5- weight the empty shell (w2)6-calculate the net weight for each capsule content by subtracting w1-w27- calculate the amount of the active ingredient in each capsule

Content uniformity

1- assay 10 units individually in the drug monograph2- e.g place one dosage unit in each of the tubes of the basket with water or any other specified medium maintained at 37°C3- shake till complete disintegration of capsules4- test for the concentration of active content, which should lies within the range of 85-115%

2- Weight variation

1- weight 20 intact capsules individually & determine the average weight2- the requirements are met if each of the individual weight is within the limit of 90-110% of the average weight

3- Disintegration test

1- place one dosage unit in each of the tubes of the basket with water or any other specified medium (depends on individual monograph) maintained at 37°C2- Observe the capsules for a time limit (specified in the individual monograph), at the end of the prescribed time, all of the capsules must have been disintegrated excluding the fragments from the capsule shell3- If 1 or 2 capsules fail, the test should be repeated on an additional 12 capsules Then, not fewer than 16 of the total 18 capsules tested should disintegrate completely

4- Dissolution test

1- Place each of the capsules in the dissolution apparatus, Operate immediately at a specified rate within specified dissolution medium at 37°C Aliquots should be withdrawn at a specified time and concentration of A.C is calculated1- At stage 1: when 6 capsules are tested, the amount of each of the dissolved content should not be less than 5 of the mentioned in the monograph2- At stage 2: when 6 capsules are tested, the average of 12 (both from step 1 and 2 should be equal to or greater than 15%3- At stage 3: when 12 capsules are tested, the average of 24 capsules (all 1,2 and 3 steps) should be equal to or greater than 15% amount of each of the dissolved content should be in the range 85-115%