The present study aims to develop MTX-S (Methotrexate sodium) in situ gels as an effective way for the treatment of Rheumatic Arthritis (RA). Methotrexate has been reportable to cause vertebrate death and/or inherent anomalies. Therefore, it's not suggested for ladies of childbearing potential unless there's clear medical proof that the advantages are often expected to outweigh the thought of risks. Pregnant girls with skin condition or atrophic arthritis mustn't receive methotrexate sodium. methotrexate sodium causes hepatotoxicity, pathology and liver disease, however usually solely when prolonged use. Acutely, liver catalyst elevations ar ofttimes seen. These ar sometimes transient and symptomless, and additionally don't seem prophetic of consequent internal organ illness. Liver diagnostic assay when sustained use usually shows microscopic anatomy changes, and pathology and liver disease are reported; these latter lesions might not be preceded by symptoms or abnormal liver perform tests within the skin condition population. For this reason, periodic liver biopsies ar sometimes suggested for psoriatic patients UN agency ar beneath long-run treatment. Persistent abnormalities in liver perform tests could precede look of pathology or liver disease within the atrophic arthritis population. Like different cytotoxic medicine, methotrexate sodium could induce “tumor lysis syndrome” in patients with chop-chop growing tumors. applicable adjunct and medicine measures could forestall or alleviate this complication. methotrexate sodium given concomitantly with radiation therapy could increase the danger of soppy tissue sphacelus and osteonecrosis. diarrhoea and lesion rubor need interruption of therapy; otherwise, hurt redness and death from enteric perforation could occur. The in situ gels composed of Pluronic F-127 as a polymer and Hydroxy Propyl Methyl Cellulose K4M (HPMC K4M) and Polycarbophil (PCL) as copolymers were manufactured by cold method. Acyclovir (ACY), a wide used antiviral drug, could be a artificial purine ester analog derived from purine. it's effective within the treatment of herpes simplex virus (HSV), principally HSV one and HSV two, and pox herpes. medicine exerts its antiviral activity by competitive inhibition of microorganism deoxyribonucleic acid through selective binding of medicine to HSV-thymidine enzyme .Currently obtainable dose varieties of medicine square measure meant for blood vessel, oral, and topical administration. general delivery of the drug following administration by these routes is way from optimum. However, the oral absorption of medicine is dose dependent and extremely variable with bioavailability starting from fifteen to half-hour The transdermic penetration is poor; and since of its restricted solubility in water (1.62 mg/mL at 22°C) it can not be given as eye drops or by shot. As channel administration medicine is presently obtainable as infusion or as bolus shot within the sort of sturdy alcalescent (pH 10-11) answer of Na salt. Consequently, administration of this dose kind could cause phlebitis or perivascular inflammation There are several makes an attempt for up the chemistry properties of medicine by chemical modifications that square measure documented within the literature. These embrace victimization medicine as prodrug, using novel redox-based chemical targeting systems to reinforce ocular, parenteral, nasal, and connective tissue delivery of drug for bigger oral bioavailability. attributable to its poor oral and stratum absorption of medicine, oral mucous membrane could be a logical selection for native and general delivery .There square measure many reasons thanks to that oral mucous membrane is a pretty website for the delivery of therapeutic agents that embrace its accessibility, wonderful blood offer, by-pass of internal organ first-pass metabolism, speedy repair, and porousness profile. The limitation of oral membrane drug delivery is that the dilution and speedy elimination of locally applied medication thanks to the flushing action of spit. The delivery system within which the drug is incorporated is so a very important thought and may be developed to prolong the retention of the drug within the rima. Bioadhesive polymers are utilised in gel forms to prolong the continuance on oral mucous membrane and to scale back the frequency of application and also the quantity of drug administered. This may improve patient’s compliance and acceptance of the drug product.