JOINT PAIN AND ARTHERITIS

Arthritis is derived from the Greek term “disease of the joints.”It is defined as an acute or chronic joint inflammation that often co-exists with pain and structural damage. Artheritis is not synonymous with arthralgia, which refers to pain localizeds to a joints, regardless of the origin of the pain (which may or may not be due to joint inflammation). There are several different types of artheritis, with management being different for each. History and physical examination are crucial in recognizing the type of artheritis, while additional laboratory and imaging may sometimes be necessary of confirming the diagnosis. This activity outlines the evaluation and treatment of artheritis and explains the role of the interprofessional team in managing patients with this condition. Arthritis is the swelling and tenderness of one or more of your joints. The main symptoms of arthritis are joint pain and stiffness, which typically worsen with age. Although theres no cure for arthritis, treatment have improved greatly in recent years and, for many types of artheritis, particularly inflammatory artheritis, theres a clear benefit in starting treatment at an early stage. Cartilage is a firm but flexible connective tissue in your joints. It protects the joints by absorbing the pressure and shock created when you move and put stress on them.1 Arthritis represents one of the most prevalent chronic health problems and is a leading cause of disability. More than 40 millions people in the india have artheritis or chronic joint symptoms that are often accompanied by joint pain. By the year 2020, this number is expected to reach 60 million. The most common form of artheritis is osterartheritis affecting an estimated 21 million aduld in the india. Other common artheritis condition include rheumatoid arthritis and gout. Arthritis is the inflammation of a joint, which can include infiltration of inflammatory cells (monocytes), synovial hyperplasia, bone erosion and formation, narrowing of the joint space, and ankylosis of the joint. The most common form of arthritis is osteoarthritis . osteoarthritis is a degenerative disease characterized by damage to the articular cartilage, changes in subchondral and marginal bone, synovitis and capsular thickening, typically affecting weight bearing joints (knee and hips). Pain in osteoarthritis is located and use-related, occurring during movement or weight bearing. Rheumatoid arthritis is an autoimmune disease of the synovium that leads to an inflammatory poly-arthritis. It is characterized pattern of affected joint and by morning stiffness, joint swelling and tenderness. Pain in rheumatoid arthritis improve with movement. Gout represent one of the most painful forms of arthritis. A metallic disorder with high blood levels of uric acid. The metatarsophalangeal joint (big toe) is typically affected, but other joints can be invoved as well, including the knee. A reduction in the normal amount of its cartilage tissue causes some forms of arthritis.[2]

• Osteoarthritis                    
• Rheumatoid arthritis (RA)
• Gout
• Septic arthritis
• Inflammatory mono-arthritis

Osteoarthritis:

Osteoarthritis is a chronic, degenerative disorder of unknown cause characterised by gradual loss articular cartilage. It is the most prevalent disease in our society, with a worldwide distribution. It ranks fourth in health impact in woman and eight in men in the western world.[3]

Symptoms:

1. Mild Swelling
2. Pain in Joints (Hipes, knee and Hands are most common)
3. Stiffness

Rheumatoid Arthritis:

Rheumatoid Arthritis is a chronic, systemic, inflammatory autoimmune disorder causing symmetrical polyarthritis of large and small joints, typically presenting between the ages of 30 and 50 year. The most common inflammatory arthritis, it afflicts an estimated 25 men and 54 women per 100,000 population and is responsible for 250,000 hospitalizations and 9 million physician visits in the UA each year.[4]

Symptoms:

1. Painfull
2. Affects Joint Lining

Gout

Gout is a disease condition which often is considerd as a form of inflammatory arthritis. Unlike arthritis, gout is not a degenerative process. Its generally characterized by frequent attacks of swelling, redness, and a tender, warm and puffy expression of bone joint areas. (5)

Symptoms:

1. Redness and swelling in joints
2. Stiffness.

TRANSDERMAL PATCHES

Transdermal drug delivery systems (TDDS), also known as “patches,” are dosage forms designed to deliver a therapeutically effective amount of drug across a patient’s skin. In order to deliver therapeutic agents through the human skin for systemic effects, the comprehensive morphological, biophysical and physicochemical properties of the skin are to be considered. Transdermal delivery provides a leading edge over injectables and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Transdermal delivery not only provides controlled, constant administration of the drug, but also allows continuous input of drugs with short biological half-lives and eliminates pulsed entry into systemic circulation, which often causes undesirable side effects. The TDDS review articles provide valuable information regarding the transdermal drug delivery systems and its evaluation process details as a ready reference for the research scientist who is involved in TDDS. With the advancement in technology Pharma industries have trendified all its resources. Earlier we use convectional dosage form but now we use novel drug delivery system. One of greatest innovation of novel drug delivery is transdermal patch. The advantage of transdermal drug delivery system is that it is painless technique of administration of drugs. Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems.[6]

Advantages

1. First pass metabolisms of drug get avoided.
2. Gastrointestinal incompatibilities get avoided.
3. Self-medication is possible.
4. Duration of action gets extended & predictable.
5. Unwanted side effects get minimized.
6. Number of doses get reduces which improve patient compliance.

Disadvantages

1. Chances of allergic reactions at the site of application like- itching, rashes, local edema  etc.
2. Larger molecular size of drug (above 1000) creates difficulty in absorption.
3. Barrier function of skin varies from site to site on the same or different person.
4. Drug with hydrophilic character is less suitable as compare to drug with lipophilic character because of their low permeability.[7]

Types of transdermal patches

1. 1. Single-layer Drug-in-Adhesive:

The adhesive layer of this system also contains the drug. In this type of patch the adhesive layer not only serves to adhere the various layers together, along with the entire system to the skin, but is also responsible for the releasing of the drug. The adhesive layer is surrounded by a temporary liner and a backing.

1. 2. Multi-layer Drug-in-Adhesive:

The multi-layer drugin adhesive patch is similar to the single-layer system in that both adhesive layers are also responsible for the releasing of the drug. The multi-layer system is different however that it adds another layer of drug- inadhesive, usually separated by a membrane (but not in all cases). This patch also has a temporary liner-layer and a permanent backing.

1. 3. Reservoir:

Unlike the Single-layer and Multi-layer Drug-inadhesive systems the reservoir transdermalsystem has a separate drug layer. The drug layer is a liquid compartment containing a drug solution or suspension separated by the adhesive layer. This patch is also backed by the backing layer. In this type of system the rate of release is zero order.

1. 4. Matrix:

The Matrix system has a drug layer of a semisolid matrix containing a drug solution or suspension. The adhesive layer in this patch surrounds the drug layer partially overlaying it.

1. 5. Vapour Patch:

In this type of patch the adhesive layer not only serves to adhere the various layers together but also to release vapour. The vapour patches are new on the market and they release essential oils for up to 6 hours. The vapours patches release essential oils and are used in cases of decongestion mainly. Other vapour patches on the market are controller vapour patches that improve the quality of sleep. Vapour patches that reduce the quantity of cigarettes that one smokes in a month are also available on the market.[6]

Human skin comprises of three distinct but mutually dependent tissues: The stratified, vascular, cellular called as “epidermis” Underlying dermis of connective tissues, Hypodermis.

Epidermis

The multilayered epidermis varies in thickness, depending on cell size and number of cell layers of epidermis, ranging from 0.8 mm on palms and soles down to 0.06 mm on the eyelids. Stratum corneum. This is the outermost layer of skin also called as horny layer. It is approximately 10 mm thick when dry but swells to several times this thickness when fully hydrated. It contains 10 to 25 layers of dead, keratinized cells called corneocytes. It is flexible but relatively impermeable. The stratum corneum is the principal barrier for penetration of drug. The architecture of horny layer may be modeled as a walllike structure. In this model, the keratinized cells function as protein “bricks” embedded in lipid “mortar.” The lipids are arranged in multiple bilayers.

Dermis

Dermis is 3 to 5 mm thick layer and is composed of a matrix of connective tissue, which contains blood vessels, lymph vessels and nerves. The cutaneous blood supply has essential function in regulation of body temperature. It also providesnutrients and oxygen to the skin while removing toxins and waste products. Capillaries reach to within 0.2 mm of skin surface and provide sink conditions for most molecules penetrating the skin barrier. The blood supply thus keeps the dermal concentration of a permeate very low and the resulting concentration difference across the epidermis provides essential concentration gradient for transdermal permeation.

Hypodermis

The hypodermis or subcutaneous fat tissue supports the dermis and epidermis. It serves as a fat storage area. This layer helps to regulate temperature, provides nutritional support and mechanically protection. It carries principal blood vessels and nerves to skin and may contain sensory pressure organs. For transdermal drug delivery, drug has to penetrate through all these three layers and reach into systemic circulation while in case of topical drug delivery only penetration through stratum corneum is essential and then retention of drug in skin layers is desired.[6]

Components of transdermal patches

1. 1. Polymer Matrix

The polymer controls the release of the drug from the device. The following criteria should be satisfied for a polymer to be used in transdermal patches.

1. Molecular weight, chemical functionality of the polymer should be such that the specific drug diffuses properly and gets released through it.
2. The polymer should be stable.
3. The polymer should be nontoxic
4. The polymer should be easily of manufactured
5. The polymer should be inexpensive
6. The polymer and its degration product must be non-toxic or non- antagonistic to the host.
7. large amounts of the active agent are incorporated into it.

Types of polymers: -

1. 1. Natural polymers: Cellulose derivative, Gelation, Waxes, Proteins, Gum, Shellac, Natural rubber,starch.
   2. Synthetic Elastomers: Hydrin rubber, silicone rubber, Nitrile, Acrylonitrile, Neoprene.
   3. Synthetic polymers: Polyvinyl alcohol, polyvinyl          chloride, polyethylene, polypropylene, polyamiode, polyurea, epoxy.

1. 2. Drug: -

Drug solution in direct contact with release liner. Physiochemical properties: -

1. The drug should have a molecular weight less than 1000 Daltons.
2. The drug should have affinity for both lipophilic and hydrophilic phases.
3. The drug should have a low melting point.

Biological properties

1. The drug should be potent with a daily dose of the order of a mg/day.
2. The half life (t½) of the drug should be short.
3. The drug must not produce allergic response.
4. Tolerance to the drug must not develop under the near zero-order release file of transdermal patches.

       
           
       
    Fig.3 : Different parts of transdermal patch[10]

1. 3. ---

      Permeation Enhancer: -

The flux J. of drug across the skin can be write

As J = D dc/dx

J = the Flux

D = diffusion coefficient

C = Concentration of the diffusing spectes X = Spatial coordinate

Solvent: -

These compounds increase penetrationpossibly by swelling the polar pathway. e.g.: Water alcohols–Methanol & ethanol, / Dimethyl acetemide Propylene glycol and Glycerol.

 Surfactants: -

The ability of a surfactant to alter penetration is a function of the polar head group and the hydrocarbon chain length.

1. 1. Anionic surfactant:- Sodium lauryl sulphate Diacetyl sulphosuccinate
   2. Nonionic Surfactant:- Pluronic F127, Pluronic F68
   3. Bile Salt: - Sodium taurocholate, Sodium deoxycholate.

Miscellaneous Chemicals: -

These include urea, a hydrating and keratolytic agent; N, N dimethyl-mtoluamide; calcium thioglycolate; anticholinergic agents. Some potential permeation enhancers have recently been described but the available data on their effectiveness sparse. These include eucalyptol, di-omethyl-ß-cyclodextrin and soyabean casein

Enhance the permeation e.g. Urea, calcium thioglycolate. 7.4 Other excipients: -

Adhesives: -

The pressure sensitive adhesive can be positioned on the face of the device or in the back of the device.

1. 3. 1. It should not be irritant
      2. It should be easily removed
      3. It should not leave an un washable residue on the skin
      4. It should have excellent contact with the skin.
      5. Physical & chemical compatibility with the drug
      6. Permeation of drug should not affected.
   4. Linear: -

Protect the patch during storage. The linear is removed prior to use.

1. 5. Backing: -

Protect the patch from the outer environment.

MECHANISM OF ACTION OF TRANSDERMAL PATCHES

Benefits of herbal joint pain patches

1. 1. 1. Combats pain and inflammation
      2. Reduces the time it takes to heal from injuries
      3. Increases flexibility and mobility

Herbal ingredients which are used in formulation

1. Kalonji Oil

Synonyms: -

Black cumin

Biological Source: -

Nigella Sativa (black caraway also known as black cumin, Nigella, kalonji,) is an annual flowering plant.

Family: -

Ranunculaceae.

Chemical constituents: -

Kalonji contain about 0.4 – 0.45% volatile oil. The volatile oil of the drug contains saturated fatty acid which include: nigellone that is the only component of the carbonyl fraction of the oil, thymoquinone (TQ) thymohydroquinone (THQ), Thymol, carvacrol, volatile oil of the seed

Uses :

1. 1. Kalonji seed have anti-inflammatory properties that can treat Various chronic inflammation.
   2. It is known for healing joint pains by proving lubrication between the joint
   3. Improve creaky joints.
   4. Reduce inflammation.
   5. Accelerate weight loss

       
           
       
    Fig 5 :- kalonji oil [15)

2. ---

   Clove oil

Synonyms: -

Eugenia cariophylata

Biological source: -

Cloves consist of dried flower buds of Eugenia caryophyllus, (Family: Myrtaceae).

Chemical constituents:

clove oil contain about 15 to 20 % of volatile oil, 10% to 13% of tannis, resins, chromosomes and eugenic. The volatile oil of the drug contain eugenol 89% and 5 to 15% eugenol acetate and beta- cairofileno.

Uses

1. Relieves muscular pain.
2. Promotes faster healing.
3. Reduce irritability.[16]

       
           
       
    Fig 6 : Clove oil

1. ---

   Mustard oil

Synonymes:

Vegetable oil

Biological source:

Musterd oil obtained from natural seed of Brassica nigra Koch or Brassica juncea L. czern

Chemical constituens :

Musterd oil ha about 60% monounsaturated fatty acid (42% erucic acid & 12% oleic acid ), it has about 21% polyunsaturated fats.

Uses :

Musterd oil use as a –

• Dental analgesic
• carminatives
• Stimulants
• Aromatic

       
           
       
    Fig 7. Musterd oil[18]

4. ---

   EUCALYPTUS OIL

Synonyms:

Blue gum, genus eucalyptus, eucalyptus comphora

Biological source:

Eucalyptus oil is made from the fresh leaves and branch tops of the eucalyptus plant.

Chemical constituents :

eucalyptus oil has eucalyptol, pinene

       
           
       
    Fig 8. Eucalyptus Flower and Fruit [19,20]

Uses

1. Relieves stuffy nose.
2. Clears respiratory complaints.
3. Eases sore muscle and joint pain.
4. Post-surgery pain reliever.
5. Promotes oral health.
6. Promotes scalp health and clear lice. 7: Boosts immunity.

4.CAMPHOR

       
           
       
    Fig:9. Structure of Camphor

IUPAC Name:

1,7,7-trimethylbicyclo [2.2.1] heptan-

2-one

Molecular Formula:

C10H160

Physical Appearance:

Colour :

colourless to white

Odour:

arrogating odour

 Taste:

aromatic taste

Boiling Point:

399F at 760 mmHg

Melting point :

345F

Solubility:

Insoluble in water and Soluble in ethanol

Uses:

1. 1. Used as a plasticizer and chemical intermediate, also used as an additive to explosives, varnishes, lacquers, insecticides, fungicides, pharmaceuticals, cosmetics and flavourings.[12]
   2. It helps to heal muscular pains and aches as well as rheumatism.
   3. It also helps to decreases cholesterol levels in the body.[13]

       
           
       
    Fig 10. Menthol Camphor

       
           
       
    Fig 11. Thymol Camphor

       
           
       
    Fig 12. Natural Camphor[14

MATRIALS AND METHOD

Material

Drugs chemicals used

1. 1. 1. 1. The active pharmaceutical ingredients were prepared by combining requisite amount of camphor in Mustard oil, kalonji oil and 2-3 drops of clove oil and eucalyptus oil, is added and dissolve in ethanol.
         2. The drug matrix was prepared by dissolving HPMC and EC in methanol. To this solution Tween 80 was added and stirred.
         3. Dried at room temperature for 24hrs.
         4. The dry films were removed and wrapped in aluminium foil and kept in a desiccator until used.
         5. The so prepared films were stick to adhesive layer of bandage which was purchased from local market.

EVALUATION PARAMETERS

Physical appearance:

Physical appearance the formulated patches were found to be fear, smooth, uniform. flexible in their physical appearance and free from entrapment of air bubble

Thickness of the patch:

The thickness of the drug loaded patch is calculated in different prints by using a digital micrometre, or travelling microscope, dial gauges and determines the average thickness and standard deviation for the same to ensure the thickness of the prepared patch Paich will have an equal thickness of every points. The variation of thickness within the patch and patch to patch can be calculated.

Moisture content:

Individually weighed patches are kept in the desiccators having fused calcium chloride at room temperature for 24 hours After 24 Hours the patches are to be reweighed and percentage moisture content is calculated by the formula & Moisture content (Initial Weight-Final weight) X 100 initial weight

Moisture uptake.

The weighed films are to be kept in desiccators at room temperature for 24 hrs containing saturated solution of potassium chloride in instruct to maintain 84% RH, after 24 hrs the films are to be reweighed and determined the percentage moisture uptake from the mentioned Moisture uptake (Final weight Initial weight X 100)/Initial weight

Folding endurance:

This was determined by repeatedly folding the film at the same place until it broke the number of period the films could be folded at the same place without breaking/ cracking gave the value of folding endurance

Weight uniformity:

Weight variation is studied by individually weighing 10 randomly selected patches and calculating the average weight. The individual weight should not deviate significantly from the average weight.

Antimicrobial activity :.

Cup plate of cylinder plate method

This method relies on the diffusion of an antibiotic from a vertical cavity or a cylinder through the solidified agar layer in a petri plate. The growth of test microorganism in observe to be inhibited in a circular area or zone around the cavity containing antibiotic solution.

Steps involved in cup plate method are given below,

1. 1. 1. 1. A liquefied assay medium (43–45-degree c.) is inoculated by the suspension of test microorganism.
         2. This inoculated test culture medium poured and spread on sterile petri or preprepared agar plates.
         3. Standard and test antibiotic solution of known concentration are prepared in appropriate solutions, which are then added to sterile cavities prepared on solid medium.
         4. Uniform volume of sodium should be added to each cavity to fill them sufficiently if paper discs are used, they should sterilize first, then dipped in standard or test Cup solution and finally placed on medium surface.
         5. The plates are allowed to stand at room temperature or at 4degree c. for 1-2 hours. This is the period of pre Incubation diffusion which minimises the effect of variation time between the applications of different solutions.
         6. All plates are then incubated at temperature 32–35-degree c. for 18-24 hours.
         7. The diameters or areas of circular inhibition zone produce by standard and antibiotic solution are accurately measured.

Flatness :

A transdermal patch should possess a smooth surface and should not constrict with time. This can be demonstrated with flatness study. For flatness determination, one strip is cut from the centre and two from each side of patches. The length of each strip is measured and variation in length is measured by determining percent constriction. Zero percent constriction is equivalent to 100 percent flatness.

L2 = Final length of each strip L1 = Initial length of each strip

pH of the patch:

Apparatus baker, pH meter, stirrer, wash bottle.The pH meter was calibrated using standard buffer solution. About 1 patch dissolve in buffer solution and dissolved in 50ml of phosphate buffer and its pH was measured.

 RESULT AND DISCUSSION

Chemical test

Physical appearance

Table No:-10.Physical appearance

Weight uniformity

Weight of patches=total weight of 10 patches/10

=0.67+0.55+1.35+0.73+0.46+0.37+0.38+1.56+0.37+0.78/ 10

= 7.81/10

=0.781

Determination of pH:-

Fig 21. pH meter