PREPARATION OF VANISHING CREAM

Monday, October 10, 2011



Aim:  To prepare and submit 25gm of vanishing cream.
Chemical requirements :  Stearic acid, Potassium carbonate, borax, carbitol, Perfume and water.
Apparatus:  water bath, beaker,china dish etc.
Principle              : 
                                Vanishing cream is a particlar type of skin cream used during the day time, either alone in which it is expected to immiscible or vanish on application, or in conjunction with powder when it must serve as a foundation for the makeup providing suitable adherent base for the powder.
                                These creams are water continuous cream with low or medium oil content. Most of the formulations contain high quantity of stearic acid as the oil phase. This provides an oil phase which melts above body temperature and crystallizes in a suitable form, so as to be immiscible and gives nongreasy film, and moreover can confirm a very attractive appearance to the product.
                                These creams can be defined as stearic acid in a gel of stearate soap.
Procedure           :  
1.       Stearic acid is melted in waterbath at 700C.
2.       Potassium carbonate dissolved in water and borax is added to it then mix it thoroughly. This solution is heated to 700C.
3.       Then the solution is poured into melted stearic acid with stirring at same temperature for 10 mins until the saponification is completed.
4.       China dish is removed from the flame and stirred until it is cold.
5.       Perfume is dissolved in carbitol which is added to the cream and mixed thoroughly
Report                  :  25 of vanishing cream was prepared and submitted .

Formula              :
S.NO
INGREDIENTS
WORKING FORMULAE
1.        
Stearic acid
4.5gm
2.        
Pottasium  carbonate
0.2gm
3.        
Borax
0.05gm
4.        
Carbitol
1.25gm
5.        
Perfume
q.s
6.        
Purified water
Upto 25ml


Nonsteroidal Anti-inflammatory Drugs (NSAIDs)



Nonsteroidal anti-inflammatory drugs, usually abbreviated as NSAIDs with analgesic and antipyretic (fever-reducing) effects and which have, in higher doses, anti-inflammatory effects.
The term "Nonsteroidal" is used to distinguish these drugs from steroids, which, among a broad range of other effects, have a similar eicosanoid-depressing, anti-inflammatory action. As analgesics, NSAIDs are unusual in that they are non-narcotic.
Types of NSAIDs
There are two main types of NSAIDs: nonselective and selective.
Nonselective NSAIDs
Nonselective NSAIDs inhibit the enzymes found in the stomach, blood platelets, and blood vessels (COX-1) as well as the enzymes found at sites of inflammation (COX-2) to a similar degree. Nonselective NSAIDs include drugs such as aspirin, ibuprofen, naproxen and dichlorofenac.
Selective NSAIDs09:20:44
Selective NSAIDs (also called COX-2 inhibitors) inhibit the COX enzyme found at sites of inflammation (COX-2) more than the type of enzyme normally found in the stomach, blood platelets, and blood vessels (COX-1). Celecoxib is a selective NSAID
CLASSIFICATION OF NSAIDs
1) NONSELECTIVE IRREVERSIBLE COX INHIBITORS
                   (a) Salicylates           :          Aspirin (Acetyl-salicylic acid)
                                                                 Sodium salicylate
                                                                Methyl salicylate
                                                                 Salicylic acid
                        Others                  :          Olsalazine

2) NONSELECTIVE REVERSIBLE COX INHIBITORS
                   (a) Indole derivatives    :    Indomethacin
                                                                 Sulindac
                   (b)Propionic acid derivatives: Ibuprofen
                                                                       Ketoprofen
                                                                       Flurbiprofen
                                                                       Naproxen
                     (c)Aryl acetic acid derivatives: diclorofenac
                                                                           Aceclofenac
                     (d) Anthracitic acid: Mefenamic acid
                                                           Flufenamic acid
                      (e) Pyrazolone derivatives: Phenyl butanone
                                                                        Oxiphenbutazone
                      (f) Oxicam derivatives    : Tenoxicam
                                                                  Pyroxicam
                      (g) pyrrole-pirole derivatives: ketorolac
                                                                           Tolmethin
                                                                          Oxaprozin
3) SELECTIVE COX-2 INHIBITORS:
                                                 Celecoxib
                                                 Rofecoxib
                                                 Valdexoxib
4) WEAK INHIBITOR OF COX1&COX2
                                                          Nimusalide
5) PREFERENTIAL COX 2 INHIBITORS
                                                         Meloxicam
                                                          Ethodolac
                                                           Nabumethone
6) COX 3 INHIBITOR /REVERSIBLE INHIBITOR OF COX1
                                                           Paracetamol
                                                            Methamizol
7) OTHER NON STEROIDAL DRUGS
                                           Nefopam
3) MORE COX-2 SELECTIVE INHIBITORS
                                             Nimusalide
                                              Etodolak
                                              Meloxicam
                                              Nabumethone
4) COX-2 SELECTIVE INHIBITORS
                                            Celecoxib
                                             Etorcoxib
                                           Valdecoxib

General Mechanism of action
Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) iso enzymes. COX catalyzes the formation of prostaglandins and thromboxane from Arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. This mechanism of action was elucidated by John Vane (1927–2004), who later received a Nobel Prize for his work (see Mechanism of action of aspirin

                                       Tissue Injury
                            
           Phospholipids in cell membrane
                          PHOSPHOLIPASE A2
                               Arachidonic acid
   NSAIDS INHIBITORS (-)cox
                                                 PGG2    
                          cox
                                    PGH2      
                               
      ProstaglandinE1      prostacyclin     ThrombaxaneA2
      PGD2, PGE2, PGF2                 PGI2                               TXA2, TXB2
                
Cox-1&cox2
Cox-1 
·         Present in most tissues.
·         In the GIT, it maintains the normal lining of the stomach.
·         Involved in kidney and platelet aggregation.
Cox-2
·         Present in macrophages and monocytes.
·         Inducible.
·         Responsible for pain and inflammation.

NON SELECIVE IRREVERSIBLE INHIBITORS OF COX
ASPIRIN
Analgesia
These are the salts or esters of salicylic acid.
           Salicylic acid itself is a strong irritant.
           It is one of the oldest analgesic-anti-inflammatory drugs and is still widely used.
           It is rapidly converted in the body to salicylic acid which is responsible for most of the actions.
  Mechanism of action
·         NSAIDS inhibits cyclooxygenase which is responsible for the synthesis of prostaglandin and thromboxane
·         It also inhibits platelet aggregation
Pharmacological actions
1. Analgesic action
Aspirin is a weaker analgesic than morphine.
These are effective only in dull- aching pain of low intensity.
They do not relieve severe pain like visceral pain.
They act by preventing the integration of pain sensation in the thalamus But they do not alter the                                         emotional reaction to pain.
2. Anti-pyretic effect
Salicylates do not lower normal body temperature.
Only the elevated temperature is lowered.
Mechanism
Fever is caused by elevated levels of prostaglandin E2, which   alters the firing rate of neurons with in the hypothalamus that control thermoregulation. Antipyretics work by inhibiting the enzyme COX, which causes the general inhibition of prostanoid biosynthesis (PGE2) within the hypothalamus.PGE2 signals to the hypothalamus to increase the body's thermal set point. Ibuprofen has been shown to be more effective as an antipyretic than acetaminophen. Arachidonic acid is the precursor substrate for cyclooxygenase leading to the production of prostaglandins F, D & E. This is reset for a lower temperature by salicylates
The salicylates produce sweating which also lowers body temperature
3. Anti- inflammatory action
Aspirin exert the anti-inflammatory action at high doses 3- 6 grams /day
Signs of inflammation like pain, tenderness, swelling, vasodilatation, and leukocyte infiltration are suppressed.
Aspirin inhibits cyclooxygenase activity, it diminishes the formation of prostaglandins and modulates those aspects of inflammation in which prostaglandins act as mediators.
Aspirin inhibits inflammation in arthritis.
4. on respiration
Salicylates stimulate respiration
The stimulation is depend on the dose
Salicylates stimulates respiration directly by stimulating the respiratory Centre
5. Cardiovascular system
No effect at normal dose.
Large doses increase cardiac output to meet increased peripheral O2 demand and cause direct vasodilatation.
Toxic doses produce paralysis of vasomotor Centre and BP may fall.
6. GI Tract
Salicylates produce nausea and vomiting due to direct stimulation chemoreceptor trigger zone.
Salicylates can also cause gastric ulceration and hemorrhage.
7. Anti- rheumatic effect
Salicylates have powerful anti-rheumatic effect
This effect is produced by reducing pain and inflammation of the joints
8. Blood
Salicylates lower the erythrocyte sedimentation rate (ESR) which is high in rheumatic fever
They also decrease prothrombin level of plasma.
9. Uricosuric effect
Low doses ( 1 or 2/ g day ) may decrease the urate excretion and increase plasma urea concentration
Intermediate doses ( 2 or 3 g / day ) do not alter urate excretion.
Large doses (over 5 g / day) induce urocosuric effect and lower plasma urate levels 
10. Metabolic effects
Salicylates produce uncoupling of oxidative phosphorylation
They produce hyperglycemia and glycosuria
They inhibit the synthesis but enhance the breakdown of fatty acids
Pharmacokinetics
Aspirin is taken through oral administration they are are absorbed from the stomach and small intestine
Adverse reactions
nausea, vomiting , diarrhea , ulceration perforation ,hemorrhage, skin rashes, agranulocytosis, thrombocytopenia , plastic anemia,  headache, difficulty in hearing, drowsiness, lethargy and confusion
Therapeutic Uses
1. It is used as analgesic for light and moderate pain --- 0.3 - 0.6 g - 3 times
2. used as anti-pyretic in fever ---   0.3 - 0.6 g - 3 times
3. Used as anti – inflammatory   & anti-rheumatic & ---4 – 6 g or 75– 100   mg/kg/day in divided doses
4. Anti- platelet effect - 75 – 300 mg / day
5. Used in the treatment of the gout
6. Used in the closure of ductus artereosus

İİ. Non selective reversible inhibitor of cox
Indomethacin
It has anti-inflammatory, analgesic, antipyretic and antigout actions.
It relieves pain and reduces temperature in febrile patients.
Reduces pain and joint swelling in rheumatoid arthritis but does not modify progress.
Mechanism of action
It is a portent inhibitor of cyclooxygenase thus reducing prostaglandin synthesis
Pharmacokinetics
Orally administered, well absorbed through liver, 90% bound to plasma proteins & half-life is 4 – 6 hours
Adverse effects
Adverse effects are high.
Gastrointestinal irritation with nausea, GI bleeding, vomiting, diarrhea and peptic ulcers can occur
Hypersensitivity reactions like skin rashes, leucopenia and asthma in aspirin sensitive individuals

Drug interactions
Indomethacin blunts the diuretic action of furosemide and the anti-hypertensive action of thiazides,  beta blockers and ACE inhibitors by causing salt and water retention
Dose
25 -30 mg
Uses
Rheumatoid arthritis
Gout
Ibuprofen
It is introduced in 1969. It is propionic acid derivatives better tolerated than aspirin.
Its analgesic activity is independent of anti- inflammatory activity and has both central and peripheral effect.
Temperature is reduced in febrile patients
Mechanism of action
It is a potent inhibitor of the enzyme cyclooxygenase resulting in the blockage of prostaglandin synthesis
It also prevents formation of thromboxane A2 by platelet aggregation
It exhibits anti- inflammatory, analgesic and antipyretic activities
All have similar pharmacodynamics properties but differ considerably in potency and to some extent in duration of action
Analgesic, antipyretic and anti-inflammatory efficacy is slightly lower than aspirin
It is 99% bound to plasma proteins
Adverse effects
Nausea , Vomiting, Gastric discomfort, CNS effects, Hypersensitivity reactions.
Dose
400- 800 mg
Uses: 1. It has analgesic and antipyretic activity
              2. It is used in the treatment of gout
              3. Surgical removal of impacted tooth – a combination of ibuprofen with
                     a muscle relaxant like  chlorzoxaxone is recommended
               4. It is a drug of choice in rheumatoid arthritis because of lesser adverse effects
SELECTIVE COX-2 INHIBITORS
Celecoxib
This is highly selective inhibitor of cox2 enzyme .it is more selective towards cox-2 than the cox-1.
It does not have any inhibitory effect against TXA2 at therapeutic doses
Pharmacokinetics
Orally administered excretion via renal and rectal route
Pharmacological actions
Anti-inflammatory, analgesic, antipyretic, antiplatelet action
Adverse effects
Skin rashes, hypersensitivity, ulceration, hemorrhage, diarrhea, dyspepsia, gastric discomfort,
 Mild hypertension, edema
Contraindications
Celecoxib is contraindicated in patients prone to cardiovascular or cerebrovascular disease.
Therapeutic use
·         Used in rheumatoid arthritis.
·         Used in treatment of osteoarthritis.
COX 3 INHIBITOR /REVERSIBLE INHIBITOR OF COX1
Paracetamol
It is a Para-amino phenol derivative
It has analgesic and antipyretic effects like salicylates
Paracetamol, a metabolite of phenacetin is found to be safer and effective
It has analgesic, good antipyretic and weak anti- inflammatory properties
Due to weak PG inhibitory activity in the periphery, it has poor anti-inflammatory actions
Paracetamol is active on cyclooxygenase in the brain which accounts for its antipyretic action
In presence of peroxides present at the site of inflammation, it has poor ability  
            To inhibit cyclooxygenase
It does not stimulate respiration
It has no action on acid- base balance, cellular metabolism, cardiovascular system and platelet function
It does not produce gastrointestinal irritation and uricosuric effect
It is analgesic and antipyretic of choice especially in patients in whom salicylates or other NSAID are contraindicated
Mechanism of action
Paracetamol exhibits analgesic action by peripheral blockage of pain impulse generation.
It produces analgesic and antipyretic action by inhibiting the action of endogenous pyrogen on the hypothalamic heat regulating centers.
Its weak anti-inflammatory activity is related to inhibition of prostaglandin synthesis in the CNS.
ADME
Rapid absorption through oral administration.  30% protein binding
It is metabolized by the hepatic microtonal enzymes in liver.
Plasma half-life is 2-3 hrs. 
Effects after an oral dose last 3-5 hrs.
It is mainly excreted I urine as conjugation products of glucuronic and sulphuricacids
The ability of the infant liver for glucuronidation of Paracetamol is poor and this results in enhanced toxicity of the drug in neonates
Adverse effects
·         In antipyretic doses, Paracetamol is safe and well – tolerated
·         Nausea and rashes may occur

Dose
0.5     :- 1 g every 4-6 hrs.
Chile 6 – 12 yrs : – 250 – 500 mg every 4-6 hrs
1– 5 years: - 120 – 250 mg every 4 – 6 hrs.
Less than 3 months 10 mg / kg body weight every 4 – 6 hrs.
Maximum dose for adult: – 4 g daily 
Maximum dose for a child: - 4 doses in 24 hrs.
Acute Paracetamol poisoning
When large doses are taken, acute Paracetamol poisoning results.
Children’s are more susceptible because the ability of their liver to metabolite Paracetamol is poor.
10 – 15 grams in adults cause serious toxicity.
Symptoms
                   Nausea,
                   Vomiting,
                   Paracetamol is hepatotoxic and causes severe hepatic damage.
                   Hepatic lesions are reversible when promptly treated.
Mechanism
Small portion of Paracetamol is metabolized to toxic compound – N-acetyl – benzoquinone- imine which is inactivated generally by binding with glutathione in the liver
But when large doses of Paracetamol are taken, larger amounts of the toxic compound are fumed and glutathione in the liver is not sufficient to inactivate it
As a result the toxic metabolite now binds to hepatic proteins resulting in hepatic necrosis
Chronic alcoholics and infants are more likely to develop hepatotoxicity
Paracetamol can also cause nephrotoxicity which may result in acute renal failure in some.
Uses
·         Paracetamol is prescribed in head ache, tooth ache, backache, myalgia etc.
·         Excellent antipyretic.
·         Used in children without any risk.
·         Drug of choice in osteoarthritis.