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TITLE: DEVELOPMENT AND FORMULATION OF HERBAL ANALGESIC CREAM.Introduction: Wikipedia..Any drug which is used to obtainanalgesia is known as analgesic drug/painkiller.

Analgesic drugs act on boththe central and peripheral nervous systems by using various ways. Analgesicsare different from anesthetics, which impermanent affect, and in few conditionsfully eliminate consciousness .Drugs which is commonly used as analgesics includeparacetamol, the non-steroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, and opioid drugs such as morphine. The choice of analgesicagent depends on the severity and response to other medication; the WorldHealth Organization (WHO) pain ladder specifies mild analgesics as its firststep.

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iThe type of pain also play important role in choosing analgesic agent.Traditional analgesic agents are usually less effective in the treatment ofneuropathic pain; classes of drugs that are not normally considered analgesicsare prescribed for neuropathic pain, such as anticonvulsants and tricyclicantidepressants.iiA condition such as muscle sprains and overuse injuries, topical NSAIDs provide pain relief. Topicalpreparations are preferred over oral medications because topical preparationshave fewer side effects as compared to oral medications.iiiSome examples of analgesics are:1.Paracetamol (acetaminophen): In mild to moderate pain and fever, thismedication is used. It is also recommendedin more severe pain such as cancer pain and postoperative surgical operations.

It is a mild analgesicagent and normally safe at prescribed doses.2.NSAIDs:Are group of drugs use to decrease pain and lower fever.

When given in higherdoses NSAIDs can also reduce inflammation. In most countries NSAIDs e.g.,aspirin, ibuprofen and naproxen are available as over the counter drugs.3.COX-2inhibitors: Are drugs which are derived from NSAIDs. The cyclooxygenase enzymewhich is inhibited by NSAIDs has two types: COX1 and COX2.

Advance studiessuggested most of the adverse effects of NSAIDS are due to the blockade of COX1enzyme while the analgesic effects are due to theCOX2 enzyme.4.Opioids: Morphine, codeine, oxycodone, hydrocodone, dihydromorphine all havea similar effect on the cerebral opioid receptor system. Due to opioid toxicity(confusion, respiratory depression, myoclonic jerks and pinpoint pupils) loweropioid dose is recommended, higher dose can be recommended in opioid- tolerantindividuals.

                                                                                                                                      Researchgate..Pain is subjective in nature and is measured by patient itself byreporting its intensity and other subjective qualities .

It has been a challenge to define pain becauseit is a complex, subjective phenomenon, often caused by damaging stimuli.  In medicaldiagnosis, pain is considered as a sign of an underlying condition. Pain isnormally short-lived, continuing only as late as the harmful stimulus iseliminated or the underlying injury or pathology has cured, but some painfulstates, such as rheumatoid arthritis, peripheral neuropathy, cancer andidiopathic pain, may continue for years.

Pain can be classified based on itsduration, acute or chronic, as well as other characteristics such as intensity,region of the body involved, causes etc. Pain that is minor and normally needstreatment for not more than up to a few weeks is acute pain. Pain that lastsfor more than a one month is called chronic. Conventionally, the difference between acute and chronic pain has depend on random interval oftime from onset.                                                                                                                                  Pain is the most common cause for people to use complementary and revolutionary medicine.91 An opinion of the13 highest quality studies of pain treatment with acupuncture,published in January 2009, determined that there was small difference in theeffect of real, faked and no acupuncture.92 However, otherreviews have found some advantage.939495 Additionally, thereis provisional verification for a few herbal medicines.

96 There has been someinterest in the relationship between vitaminD and pain, but theevidence so far from controlledtrials forsuch a relationship, other than in osteomalacia, is uncertain.97In health care system, plants are significant and fundamental for eliminationand restorative purposes. The use of native herbal medicine is very old and an essential part of treatment 1.For different healthcare products, conventional medicinal herbs have used as apossible source of alternative medicine.

Rich inheritance of former culture andtechnical heritage are major sources for understanding of herbal medicines 2. Accordingto WHO guidelines, approximately 75-80% of world population still rely on herbalmedicines. Active components which are originated from plant sourcesimmediately used as therapeutic agent and medicinally active chemical constituentsare also served as lead molecule for the synthesis of  many drugs 2, 3.

The great number of   rural and poor people is getting financialadvantages from native or herbal medicines. According to WHO guidelines, around25% of modern medicines which are originated from plants sources are usedconventionally and nearly 75% of herbal drugs are discovered by doing researchon traditional medicinal herbal plants 3. Due to the increase in the use ofherbal medicines the field work and screening of plant has been increasedgradually. Inthe past years, the therapeutic use of herbal medicine is getting appreciable powerin the world. Due to toxicity and side effects associated with allopathicmedicines there is abrupt increase in the use of herbal medicine. Intraditional system of medicine, herbal medicines are used as major remedy inmedical practices since many years.

Because of biomedical advantages associatedwith herbal medicine and its societal views in many parts of the world medicalpractices continues today which made a great participation towards preservinghuman health 1. Herbal medicines are the synthesis of corrective experiences andpractice of native systems of medicine for over hundreds of years. During the pastdecades there is huge progress in medical research but still the treatment ofmany dangerous diseases including pain and inflammation is troublesome. Theanalgesic and anti-inflammatory drugs which we are using are found with some dangerousside effects; for this reason there is a need to develop such analgesic andanti-inflammatory drugs which have less side effects.

When compared withsynthetic drugs it can be seen that herbal medicine have more safety, efficacy,cultural acceptability and less side effects 27.-The number of chemicalcompounds, which are found  inside theplant kingdom are supposed to have good consistency with the human body asthese are part of the physiological events of living flora 2. Different phytoconstituentslike alkaloids, flavonoids, xanthone, coumarin, sterols, withaferin-A,andrographolide etc., are also proved efficient as analgesic andanti-inflammatory agent 5, 6. Therefore it is the need of time to exploreherbal medicine and uses them in our daily life. EXAMPLES OF HERBS USED AS ANALGESICS:Aloe Vera:                                                                                                                                                                                                                                 AloeVera can be used to achieve analgesia e.

g., reduction in pain without losingconsciousness. During dental treatments Aloe vera can be used topically forpain reduction. For moth ulcers, sores, burns, cuts, scrapes it can be usedeffectively for treatment. For quick relief of pain after dental surgicalprocedures it can be recommended. It is also used for pain healing purposes inthe treatment of piles and hemorrhoids.For arthritic pain, Aloe Vera juice is effective and has been used formany years.

Arnica:The Arnica can be used for medicinal purposes; it is applied to the skinfor soothing muscle aches, relieving sprains, reduction in inflammation,healing and bruising wounds. However, it can cause serious side effects whentaken orally. For diabetic eye damage and post-surgical operations thehomeopathic version of Arnica is used.Basil:Some varieties of Basil have analgesic activity which can be used toreduce pain on a lower level.BlackPepper:Piperine is a chemical present in black pepper it can be used for painreduction. For reduction in pain an analgesic cream can be made by mixingpiperine with other ingredients.

Cardamom:Advance research has shown that cardamom has gastro-protectiveproperties. The pain which is associated with stomach cramps and other stomachproblems can be reduced with cardamom. Painful muscle spasms in animals can bereduced with the use of cardamom.Cayenne: Capsaicin is a natural pain relieving herb which is present in super-hotcayenne.

Capsaicin reduces the amount of substance P which delivers painmessages to the brain. Capsaicin creams and patches are used for painreduction.CelerySeed:Patients with arthritis, osteoporosis and gout are treated with celeryseed extract, after few weeks it can be seen that patients reported lower painlevels and some reported complete pain relief.Chamomile:For hay fever, inflammation, muscle spasms, menstrual disorders, diaperrash, skin infection, ulcers, wounds, Chamomile can be used because it containsterpenoids and flavonoids which contribute to its medicinal properties.

Cloves:                                                                                                                                                          Cloveshave analgesic and antibacterial properties due to the presence of compoundeugenol and are considered as traditional remedy for toothache or mouth ulcers.Cloves are used in many topical preparations for the purpose of pain reductionand to reduce mouth and throat inflammation.Coriander:Coriander has analgesic properties and is used in the treatment ofhemorrhoids, toothaches and joint pain.Fennel:Studies have reported that fennel is an effective herb in menstrualpain.

Ginger:For headaches or migraine pains, ginger play important role as it canreduce pain effectively. Advance research has shown that sumatriptan and gingerhas comparable analgesic properties. Patients of osteoarthritis also can getbenefits from the use of ginger. One advantage of using ginger is that it doesnot cause any side effects like other medications.JamaicanAllspice:Jamaican Allspice can be used in both ways externally and internally formenstrual cramps, stomach pains.

Licorice:Licorice root is used for various medical conditions, used in themanufacturing of both eastern and western medicine. Patients with stomachulcers who had not get benefits with conventional medicines when used licoricefluid extract get maximum benefits and after about 6 weeks of therapy ulcersare completely removed in these patients. The itching which is associated witheczema can be minimized with the use of topical licorice gel.

The pain which iscaused by sores and mouth ulcers can stop when licorice root is gargling withwarm DGL.Marjoram:Eugenol is present in marjoram and has analgesic qualities. It is a besthome remedy for patients who have arthritis and inflammatory bowel conditions. Mustard:Mustard seeds are used in various medicinal problems; the seed haveanalgesic activity and can be recommended in muscular pain, ringworm andrespiratory disorders. Mustard seed poultice is known for its natural analgesiceffects and can be used in various painful conditions nd in muscle aches.

Neem:In itching and painful conditions neem can be used topically, it is apotent analgesic agent and provides analgesia within a short duration of time.In various medical problems like eye disorders, stomach upset, gum disease,intestinal worms etc. Neem has been used for many years.

Nutmeg:Nutmeg has analgesic properties and it has been used to treat variouspainful conditions. It can be used topically or ingested to get pain relievingproperties. Parsley:Parsley root has analgesic properties it can relax stiff joints andeliminate the pain associated with joints. Rosemary:The pain associated with heartburn, intestinal gas, gout and headachecan be relieved with the use of rosemary.

Topical preparations of rosemary areavailable which can lessen the severity which is associated with toothache,eczema and joint or muscle pain. Sage:Sage is used in teas and gargles as an herbal remedy to eliminate thepain associated with sore throats, mouth ulcers, gum disease, laryngitis andcoughs. For dental pain two tablespoons of dried sage and one tablespoon of seasalt add in water , rinse your mouth with this water you can get relief fromdental pain. SlipperyElm:Topical and oral preparations of slippery elm are used to relievetoothaches, coughs, sore throats, boils, burns and skin inflammation. Thyme:Advance research has shown that thyme has excellent analgesic effects. Itcan work better than ibuprofen .In menstrual pain the analgesic activity ofthyme is remarkable. In different aches and pains thyme can be recommended toget best pain relieving effects.

Turmeric:Curcumin is present in turmeric which is responsible for analgesicactivities. Comfrey Root:                                                                                                                                              Forthe treatment of painful joints and other painful conditions related withjoints, this root has been used traditionally in medicines for centuries.TOPICAL PREPARATIONS: Semisolid dosage forms which are made up of oil phase, aqueous phase andemulsifying agent are known as creams. Creams has high viscosity, virgincoconut oil is used for the preparation of base for cream which is oil phase, distilled water is used which servedas aqueous phase and nonionic surfactant Tween 80 is used as the emulsifyingagent. A different topical preparation e.

g., creams and gels combine distinctingredients which have analgesic activity, for a better synergistic effect. Differentcomplications are faced during the preparation of cream e.g., instability suchas creaming or sedimentation, flocculation, coalescence, Ostwald ripening(disproportionation) and phase inversion etc. For the determination ofshelf life of emulsions, stability tests such as thermal stability, freeze-thawand centrifugation testing, optical monitoring at accelerated temperatures andvaluation such as microscopic examination, pH and viscosity are done.  Glucosamine, chondroitin, celadrin, comfreyroot, capsicum, green-lipped muscle extracts are very effective naturalingredients which are used in many topical preparations.

Preformulation tests for cream: Physicochemicalproperties of a novel drug molecule are very important and significant, preformulationgroup of studies should focus on such properties as these properties couldaffect the drug presentation and the evolution of a dosage form. These studiesare very meaningful, could give significant information for formulation designand development or support the demand for molecular adaptation. The mainpurpose of preformulation studies is to create particulars helpful to theformulation in evoluting stable and bioavailable dosage forms which can be put-togetherPreformulation tests for cream include: Organoleptic tests: In organoleptictests,   we observe the color, physicalappearance, smell, taste, odor, melting point and solubility. Micromeritic properties: In micromeriticproperties we determine the bulk density, tapped density, Hausner’s ratio,angle of repose and compressibility index.Visual solubility: The visualsolubility was determined in different solvents such as distilled water,ethanol, phosphate buffer pH 6.8 etc., the solutions were checked visually fortheir clarity.

Determination of pH: For thedetermination of pH 0.5 g of the formulation was dispersed in 50 ml ofdistilled water and the pH was determined.SOME EXAMPLES OF HERBAL ANALGESIC CREAMS:Glucosaminecream:                                                                                                                      For the production ofsynovial fluid glucosamine in topical preparations provides building blocks, oilswhich mobile joints, and cartilage which cushions bones. Glucosamine in topical preparationsreduce inflammation and increase the process of tissue repair.

Glucosamine whichis found in these topical treatments is in the form of n-acetyl glucosamine,which is little to sink into skin and penetrate underlying tissues toeliminate pain. Within four weeks topical preparations which containglucosamine can greatly eliminate the pain of knee osteoarthritis. One advanceresearch on glucosaminecream found that 100% of those with arthritis of the shoulder gainedadvantage. 75% of patients with arthritis of the ankle, wrist or elbow arefound with reduction in pain and 58% of those with knee osteoarthritis aregained benefit with this topical preparation.

Chondroitincream: Chondroitinand glucosamine both are mixed together in various topical preparations.Advance research has shown that people with osteoarthritis when apply a creamcontaining both glucosamineand chondroitin producedsignificant pain reduction than a placebo cream. After 4 weeks, the activeglucosamine and chondroitin cream was 20% more potent, and after 8 weeks, itwas 80% more powerful than the placebo cream.Celadrincream:Celadrinhas an anti-inflammatory and pain relieving action. It is a mixture of waxy,cetylated fatty acids that perforate in cell membranes to ameliorate theirpliancy and elasticity.Cetylatedfatty acids are naturally found in only two sites – in sperm whale oil and in astrain of mice distinguished for their indemnity against arthritis. Theceladrin which is used in creams for joint pain is obtained frommonounsaturated fats present in olive oil. Advance studies shows that celadrinfatty acid cream when applied with menthol to knees there is significantreduction in arthritis pain and this can make better the extent of mobility.

Celadrin cream is considered best in joints pain, it makes it comfortable toclimb up and down stairs. Celadrin cream cetylated fatty acids canalso decrease muscle pain which is associated with pressure on trigger pointsin the neck.MSM cream: Sulphur is an important constituent of connective tissues and structural proteins;MSM (methyl-sulfonyl-methane) is an abundant source ofsulphur. It is needed for the recovery and better functions of muscles, jointsand ligaments, has wonderful antioxidant and anti-inflammatory activity. Comfrey cream: Comfrey root has beenused to heal wounds and fractures since long. Advance studies reveal thatcomfrey root has two active constituents: allontoin which helps in tissueregeneration and rosmarinic acid which reduces pain and eliminate inflammation.

Cream which contains comfrey root is very famous and powerful remedy for jointpain, sprains and strains. A research with 120 patients who have upper andlower back pain when used comfrey root cream thrice a day for 4 to 6 days theirseverity of pain can reduce by 95% compared with inactive placebo cream whichcan reduce pain up to 38%. Researchers have reveal that comfrey cream is betterthan a prescribed, NSAID e.g., diclofenac gel in treatment of ankle sprains; itworks rapidly and provides excellent pain reducing effects after an hourapplication.

Capsicum cream:                                                                                                                                                                                    Capsicum cream helps inpain reduction by constantly provoking nerve endings in the skin at a very lowgrade; this will expend nerve endings of neurotransmitter chemicals so theybecome less responsive and pass on small number of pain messages to the brain.This action can also decrease perception from underlying painful joints.Essential oils used in topical preparations: Menthol, Levomenthol,Eucalyptus, Camphor and Oil of Wintergreen are used in various topical preparations;these are easily absorbed into the skin and produce a chilling or meltingsensation. Wintergreen is an abundant origin of methyl salicylate, a naturalanti-inflammatory analgesic related to aspirin.    ZIZIPHUS JUJUBA: WikipediaRepresentation:It is adeciduous tree or shrub, small in diameter with height of about 5-12 meters.

Twigs are spiny, the leaves are shiny-green, ovate-acute, 2-7 centimeters talland 1-3 centimeters in width .The flowers are small, fruit is an edible ovateplum. There is only one pretentious seed which has similarity to an olive pit. Distribution:Its accurateusual distribution is unclear due to large-scale gardening, but is thought tobe in southern Asia, between Lebanon, northern India, and southern and centralChina, and perhaps also southeastern Europe though more possibly started there.

Figure 1: Leaves of Ziziphus jujuba  Kingdom Plantae Division Magnoliophyta Class Magnoliopsida Order Rosales Family Rhamnaceae Genus Ziziphus Species Z.jujuba ScientificCategorization:       Formany years Zizyphus jujuba has been used as an essential oriental folk medicine.The fruits of Z.jujuba are consumedin Asian countries as a food, food additive and flavoring agent due to its highnutritional value, the ripe fruit is also used as emollient, aphrodisiac,tonic, laxative, antiemetic, and appetizer. The seeds of Z.jujuba are used formany medicinal purposes such as  used as tonic,tranquillizer, analgesic, anticonvulsant, aphrodisiac, astringent; and are usedto cure cough, asthma, vomiting, burning sensation, biliousness, leucorrhea,and eye infections in traditional systems of medicine.

It is extensively for the treatment of anxiety, insomnia,dreaminess, and night sweats and hence considered as one of the most populartraditional Chinese medicines .Recent pharmacological research reported that itpossesses anti-inflammatory, hepatoprotective, antimicrobial, anxiolytic, andhair growth promoting effects.Bioactive essential oil, saponins, phenolic compounds, alkaloids, andpolysaccharides havebeen reported from the seeds of Z.

 jujuba. Different analyticalmethods are used for the estimation of saponins and fatty acids. The plant of Z.

jujubacontains Rutin, ?-sitosterol, Maslinic acid, Heptadecanoic acid, Tetracosanoic acid, D-glucose as main activeconstituents.Indications ofZ.jujuba:   The aim of this research was to develop and formulate theherbal cream containing petroleum ether extract of Ziziphusjujuba foranalgeisc potential.                                               .

      

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