Dipen R. Bhimani

Objective: The main objective of the current research work was development and characterization of self-micro emulsifying drug delivery system of cilnidipine which is poorly water-soluble drug. The improved solubility could offer improved dissolution as well as oral bioavailability. Method: Component excipients were selected based on the preliminary studies, capryol 90 and triacetin (1:1) selected as an oil, tween 80 selected as surfactant, transcutol p selected as co-surfactant based on the maximum solubility and better emulsification efficiency. The ternary phase diagram was constructed to identify the optimum composition of the formulation. Simplex centroid mixture design was applied for selection of optimized batch of SMEDDS. Capryol 90 and triacetin, tween 80 and transcutol p were taken as an independent variables X1, X2 & X3 respectively, while emulsification time (Y1) and % drug release at 2 minutes (Y2) were taken as dependent variables. Optimized SMEDDS was evaluated based on % transmittance, emulsification time, globule size, PDI, % drug release, and cloud point. After that, SMEDDS were filled in capsule and short-term stability study was done and SMEDDS compared with pure drug for dissolution profile. Result and Discussion: Optimized batch containing capryol 90 and triacetin (1:1), tween 80 and transcutol p at a concentration of 10%, 67% and 23% respectively. The solubility of cilnidipine is increased by using capryol 90 and triacetin (1:1) as an oily phase. All the evaluation parameters of the optimized SMEDDS were met the acceptance criteria. Optimized batch of SMEDDS showed > 90% drug release within 2 minutes. Dissolution was improved as compared to the pure drug. Conclusion: A self-micro emulsifying drug delivery system of cilnidipine was developed successfully. Present work demonstrated for improving the dissolution of cilnidipine. This may lead to improved oral bioavailability of cilnidipine for the treatment of hypertension. Keywords: Cilnidipine, SMEDDS, Solubility, Dissolution enhancement.

Rheumatoid arthritis (RA) is one of the most common inflammatory disorders affecting the population worldwide. Herbal treatments are gaining popularity as complementary alternative medications among patients due to their potential benefits and minimal side effects. Biophytum sensitivum is known traditionally to possess a wide spectrum of medicinal properties and used in various inflammatory diseases such as asthma, ulcerative colitis and arthritis. The methanolic extract of Biophytum sensitivum is reported to have inhibitory action on proinflamatory cytokines (TNF-α, IL-1b, IL-6) and NF-Kb. The methanolic extract of Biophytum sensitivum also Possess angiostatic property (angiogenesis, play a significant role in pathogenesis of reumatoid arthritis). On the basis of above mentioned facts, the present study is undertaken to evaluate the anti-arthritic potential of methanolic extract of whole plant of Biophytum sensitivum in Freund’s adjuvant induced arthritis in rats. The methanolic extract of whole plant of Biophytum sensitivum (MeBS) was prepared. Rats were divided into six groups having six rats in each group. Group 1 served as vehicle control and received saline solution 2ml/kg. All the other groups had received 0.1 ml injection of Complete Freund’s Adjuvant at sub plantar region of left hind paw of rat to induce arthritis experimentally. A time period of 7 days was given for induction of arthritis. After 7 days, rats were started on various drug regimens that were continued upto 3 weeks. Group 2 which is assigned as disease control had received only CFA injection (0.1ml) on day 1.Group3 which is standard group had received methotrexate (50µg/kg/week, p.o.). Group 4, 5 & 6 were treatment groups and had received MeBS (100,200& 400mg/kg/day, p.o.), respectively. Anti- arthritic potential of MeBS was evaluated by Complete Freund’s adjuvant induced arthritis model. Assessment of body weight, paw thickness and paw volume in both hind limbs (i.e CFA injected and CFA non injected left and right hind paw respectively), arthritic swelling, inflammatory markers, radiological and histopathological examination were carried out. Methanolic extract of Biophytum sensitivum (MeBS) showed significant reduction (p<0.05) in paw thickness, paw volume of both hind limbs and in arthritic swelling. MeBS also showed significant reduction (p<0.05) in levels of inflammatory markers such as Rheumatoid factor, C-Reactive protein and Erythrocyte Sedimentation Rate. Radiological and histopathological examination supported the anti- arthritic effect of MeBS. The findings of present study reveals that MeBS (400mg/kg) shows beneficial effects against CFA induced arthritis model of rats. Keywords: Rheumatoid arthritis, CFA, Methanolic extract of Biophytum sensitivum.

The present study was conducted to evaluate the effect of methanolic extracr of B.sensitivum on mast cell Degranulation induced by Egg albumin, the antioxidant activity, differential WBC count in BAL fluid and histopathology of lungs in ovalbumin induced lung inflammation in an animal model of asthma. The methanolic extract of aerial part of Biophytum sensitivum (MBS) was prepared. Animals were divided into 6 groups (Normal control, Disease control, Standard group (Dexamethasone-4mg/kg) and Treatment groups (MBS-100 mg/kg, 200 mg/kg, and 400 mg/kg) in Ovalbumin induced model. Ovalbumin was given by i.p on days 7 and 14, by aerosol on days 28 to 30. Treatment groups and the Standard group were treated orally for last 10 days with MBS (100 mg/kg, 200 mg/kg and 400 mg/kg) and Dexamethasone (4mg/kg) respectively. In Egg albumin induced mast cell degranulation model, mast cell derived from mesentery divided into 6 groups including MBS at doses 50 µg/gm, 100 µg/gm, 200 µg/gm. Percentage protection of mast cells was calculated. Antioxidant activity was done for lung homogenate. Results were analyzed by using one way ANOVA. Methanolic extract of Biophytum sensitivum (400mg/kg) significantly (p<0.05) inhibitied the lung inflammatory cells like Total WBC, Eosinophils, Neutrophils which show the inhibition of lung inflammation in asthma model. MBS showed significant protection in mast cell degranulation induced by Egg albumin. Animal treated with MBS showed the higher level of Catalase, SOD, GSH and lower level of Nitrite than those observed in disease group. As compare to disease group, MBS treated group of animals showed protective effect in lung histopathology. It can be concluded that Methanolic extract of Aerial part of Biophytum sensitivum has protective effect on lung inflammation in experimental animals. Keywords: Lung inflammation, Asthma, Ovalbumin, Biophytum sensitivum

The main objective of present research work was to design, development and characterization of glutathione lyophilized injection. Component excipients were selected based on the preliminary studies. Solubility trials were done to determine the solubility of Glutathione in water with different concentration of sodium bicarbonate. Then glutathione injection was formulated and lyophilized by setting the lyophilization cycle parameters. But, when glutathione was lyophilized alone the cake collapse was observed. So, in order to overcome this problem lyoprotectants (mannitol, lactose, trehalose and sucrose) were added in different concentration i.e. 5% and 10%. The lyophilization cycle was developed for these formulations by changing the process parameter. After formulation development, lyophilization cycle was optimized by reducing the total cycle time. Cycle time reduced at the initial stage of primary drying till the formulation remained stable. First stage of primary drying was reduced to 2520 minutes where the cake remains elegant. The batch L1 developed by FD cycle 11 with 5% trehalose having total lyophilization cycle time 59.75 hours was considered as optimized formulation because it exhibited a good cake formation and pH, moisture content, reconstitution time and assay was found within the range of desired product profile. Short term stability studies were conducted for the optimized formulation as per ICH guidelines for a period of 30 days which revealed that the formulation is stable. It was conclude that the lyophilization technique proves to be an advantage for development of stable injectable dosage form of Glutathione. Keywords: Glutathione, Lyophilized Injection, Injectable Dosage Form.

The main objective of the current research work was to formulate and evaluate taste masked effervescent tablet. Dicyclomine HCl is very bitter in taste. The purpose of this research was to reduce the bitterness of Dicyclomine HCl using Hydroxyl Propyl Betacyclodextrin by inclusion complex method and formulate effervescent tablet with sufficient mechanical integrity and to achieve faster disintegration in the water.: Components excipients and Dicyclomine HCl HP- Betacyclodextrin inclusion complex were selected based on preliminary studies. A comparative evaluation of the taste masking was carried out for developed formulation. Citric acid, tartaric acid, sodium bicarbonate was used in 1:2:3.44 ratio for effervescent mixture. 32full factorial design was applied. Ratio of citric acid and hardness were taken as independent variables dissolution of Paracetamol and Dicyclomine HCl at 5 minutes, disintegration time, and friability were taken as dependent variables. Optimized formulation was then evaluated for general tablet evaluation and dissolution. Short term accelerated stability studies were performed for tablets prepared using optimized formulation. Optimized batch composition had ratio of Paracetamol: citric acid and hardness at concentration of 1:0.45 (mg) and 8 (kg/cm2) respectively. All the evaluation parameters of the optimized batch met the acceptance criteria. The taste masked effervescent tablet of Paracetamol and Dicyclomine HCl was formulated successfully by wet granulation method. Keywords: Paracetamol, Dicyclomine HCl, Taste masking, Effervescent tablet, Wet granulation.

The main objective of the present investigation was to formulate and evaluate chronomodulated pulsatile drug delivery system of Trimetazidine Hydrochloride which was aimed to release the drug after lag time (6 hrs) in order to mimic circardian rhythm of Angina Pectoris.Preformulation studies and compatibility studies were carried out for drug and excipients. Core tablet was prepared by direct compression using sodium starch glycolate as superdisintegrant and press coated with different polymer & varying its ratio. Further prepared tablets were optimized using 32 full factorial design. Nine batches were prepared varying the amount of polymer and ratio of polumer (HPMC K4M: EC) and they were evaluated for precompressional and postcompressional tests. Optimized batch was derived statistically using desirability function (Minitab 17).The Model was validated by formulating the check point batch. Accerelated stabilitiy study was carried out of optimized batch. Preformulation and compatibility studies was carried out using FTIR , DSC which shows satisfactory results, no interaction was found between drug and excipients. Press coating of core tablet with the combination of HPMC K4M and EC was found to be providing the desired release. Results of precompressional and postcompressional was found to be within the limits. Varying  the amount of coating and ratio of polymer have significant effect on lag time(Y1) as well as on time required for 90% drug release (Y2).Optimized batch shows lag time of 6 hrs followed by complete release within 1 hrs which is desiered in case of pulsatile delivery. No significant bias was found between predicted and observed value of check point batch.The data of stability study revealed that the optimized formulation is stable. Pulsatile drug delivery system of Trimetazidine Hydrochloride for chronomodulated therapy can be prepared by press coating technique using 200 mg of coating and HPMC K4M:EC(10:90) ratio of polymer which will provide lag time of 6hrs and complete release within 1 hrs.

A major problem in ocular therapeutics is the attainment of optimal drug concentration at the site of action, which is compromised mainly due to precorneal loss resulting in only a small fraction of the drug being ocularly absorbed. Brimonidine tartrate is an antiglaucomic agent which shows rapid precorneal exclusion and reduced ocular bioavailability when given in form of conventional ophthalmic formulations. The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions may be overcome by the use of in-situ gel forming ophthalmic systems that are instilled as drops into the eye and undergo a sol–gel transition in the cul-de-sac. In the present study, environmentally responsive ophthalmic drug delivery system composed of two gelling polymers with different phase transition mechanisms was developed. Combination of polyacrylic acid (carbopol 934P) and xanthan gum was investigated as ophthalmic vehicle. Different ratios of these polymers were used to prepare environmentally responsive ophthalmic drug delivery system by simple mixing procedure. Developed formulation was assessed for various evaluation parameters such as appearance/clarity, pH, gelation, drug content, rheological measurement, in-vitro release, and sterility testing and stability study. Prepared formulation showed agreeable appearance/clarity, acceptable pH and good gelation property. In-vitro studies demonstrated adequate drug content, desired rheological behaviour and reasonable in-vitro drug release property. Formulation was stable over one month period. In conclusion, the optimum concentration of polymers results in minimized drug loss and sustained drug release. On the basis of these findings, prepared in-situ gel may be considered as a viable alternative to conventional brimonidine tartrate eye drops.