DISCRIMINATORY POTENTIAL OF BIPHASIC MEDIUM OVER COMPENDIAL AND BIORELEVANT MEDIUM FOR ASSESSMENT OF DISSOLUTION BEHAVIOR OF TABLETS CONTAINING MELOXICAM NANOPARTICLES

ABSTRACTObjective: Dissolution test serves as a quality control tool for assessment of drug release from dosage form as well as a research tool to optimize newformulations. The existing guidelines by FDA, EMA, ICH, USP, etc., describe specifications for the dissolution of immediate release as well as modifiedrelease oral dosage form. However, none of them have discussed about the discriminatory potential of the medium to differentiate release profile of twoor more products that are pharmaceutically equivalent. It is pertinent to add here that the pharmaceutical equivalents are not always bioequivalent.Hence, a discriminatory dissolution procedure is a must requirement to differentiate the release behavior of drug from a pharmaceutically equivalentproduct that contains different types and amount of excipient in the formulation. This also becomes more cumbersome when it is desirable forprediction of in vivo behavior of a drug when it is converted into a novel delivery system like nanoparticles. The reason could be the presence ofexcipients used to formulate drug nanoparticles into solid oral dosage form, may change the drug disintegration as well as dissolution behavior, whichultimately may lead to altered bioavailability.Methods: In this study, the nanoparticles of meloxicam were prepared using wet media milling and the milled samples were dried using spray drier.The dried nanoparticles were converted into tablet dosage form by varying the type of diluent. To one batch lactose was used and another one wascontaining dicalcium phosphate (DCP). The assessment of release of meloxicam from these two batches was evaluated in various dissolution media.Results: The study revealed that in all the cases the nanoparticulate tablets of Batch 1 have given increased dissolution profile as compared tomarketed formulation (Muvera), Batch 2 and controlled tablets of meloxicam. This proved that the excipients also play a major role in the releasebehavior of drug otherwise if it was not so, the nanoparticulate tablets of Batch 1 and Batch 2 would have given the same dissolution profile in all thetried media. Batch 1 containing lactose with a higher surface area provided more and rapid wetting of the drug by the dissolution media compared toBatch 2 that contained DCP as a major diluent.®Conclusion: Among all the dissolution media tried to evaluate the discriminatory power and simulation with a biorelevant medium, the biphasicmedium of pH 1.8, 4.8 and 6.8 has promised to simulate with biorelevant media. However, the medium of pH 6.8 has shown the best dissolution profile.Keywords: Solubility, Compendial media, Biphasic media, Dissolution, Meloxicam

INFLUENCE OF FORMULATION PARAMETERS ON DISSOLUTION RATE ENHANCEMENT OF PIROXICAM USING LIQUISOLID TECHNIQUE

ABSTRACTObjective: This study revealed formulation of a liquisolid system of poorly soluble piroxicam to enhance its dissolution rate. To formulate a liquisolidsystem loaded with piroxicam, solubility study was carried out in various non-volatile liquids.Methods: In 1 ml of polyethylene glycol (PEG) 600, 100 mg piroxicam was added and stirred with gentle heating. To the above liquid medication, 1 gmicrocrystalline cellulose (MCC) 102 (as MCC has given better results), 1 g Syloid 244 FP, 2 g PEG 4000, 500 mg aerosil 200, and 0.255 g sodium starchglycolate (SSG) (5%) were added and mixed properly. The blend was compressed and subjected for quality control parameters.Results: Among all the non-volatile liquids evaluated, piroxicam was most soluble in PEG 600. Using this as liquid medication, several liquisolid compactswere prepared by varying the ratios of MCC PH 102 as carrier and Syloid 244FP as coating material and evaluated for precompression studies. To furtheraccelerate the release of drug, various additives were added in the formulation. Among them, PEG 4000 has shown better flow as well as compressionproperties. Hence, the final formulation (LS-16B) was prepared using a combination of MCC PH 102, Syloid 244 FP, PEG 4000 and SSG as superdisintegrant.The dissolution studies revealed that about 92.18% drug got released from liquisolid compacts in 120 minutes, whereas only 68.16% release wasobserved for pure piroxicam. X-ray diffraction and scanning electron microscopy images revealed the successful formation of liquisolid system.Conclusion: It was concluded that dissolution rate of poorly soluble piroxicam could be enhanced using liquisolid technique.Keywords: Piroxicam, Polyethylene glycol 600, Microcrystalline cellulose PH 102, Syloid 244 FP, Polyethylene glycol 4000

FORMULATION, SYSTEMATIC OPTIMIZATION, IN VITRO, EX VIVO, AND STABILITY ASSESSMENT OF TRANSETHOSOME BASED GEL OF CURCUMIN

Objectives: The current work presents a formulation of curcumin-loaded transethosome (CRM-TE) in the form of a gel and its characterization.Methods: Thirteen formulations were prepared by varying the concentration of Phospholipon 90G as lipid, ethanol, and ratio of lipid: Span using Box- Behnken Design. The optimized formulation was characterized by vesicle size, entrapment efficiency, drug retention, drug permeation through skin, and morphology. Parameters of CRM-TE were compared to other vesicular systems that include liposomes, ethosomes, and transfersomes. Optimized CRM-TE was incorporated into gels, and comparative evaluation was performed. CRM-TE gel was kept at 5±3°C, 25±3°C, and 40±3°C for 180 days, further evaluated for entrapment efficacy and vesicle size.Results: CRM-TE showed 286.4 nm vesicle size, 61.2% entrapment efficiency, 19.8% drug retention, and 71.3% drug permeation at 24 h in the skin. It was found superior in terms of all the parameters as compared to other vesicular formulations. CRM-TE gel also exhibited best characteristics in terms of entrapment efficiency, drug retention, and drug permeation. CRM-TE gel exhibited better stability at 5±3°C in terms of vesicle size and entrapment efficiency as compared to other storage conditions.Conclusion: CRM-TE gel could offer efficient delivery of curcumin through topical route

DESIGN AND PERFORMANCE VERIFICATION OF NEWLY DEVELOPED DISPOSABLE STATIC DIFFUSION CELL FOR DRUG DIFFUSION/PERMEABILITY STUDIES

Objectives: The present study describes a disposable static diffusion cell for in vitro diffusion studies to achieve better results as compared to well existing Franz diffusion cell (FDC) in terms of the absence of bubbles, variable receptor compartment, ease of handling, and faster results.Materials and Methods: The cell consists of a cup-shaped donor compartment made of semi permeable that could be either cellophane membrane or, animal skin fitted to a rigid frame, which is supported on a plastic plate that contains a hole for the sample withdrawal. The receptor compartment is a separate unit, and it could be any container up to 500ml volume capacity. The most preferred receptor compartment is glass beaker. In the present study, goatskin was used as semi-permeable membrane and verification of its performance was carried out through diffusion studies using gel formulations of one each of the four-selected biopharmaceutical classification system (BCS) class drugs. Metronidazole, diclofenac sodium, fluconazole, and sulfadiazine were used as model drugs for BCS Class I, II, III, and IV, respectively.Results: The newly developed diffusion cell (NDDC) was found to provide faster and more reproducible results as compared to FDC. At the time interval of 24 h, the cell was found to exhibit a higher diffusion of metronidazole, diclofenac sodium, fluconazole, and sulfadiazine by 0.65, 0.65, 0.32, and 0.81 folds, respectively. The faster release obtained with NDDC was attributed to a larger surface area of skin as compared to that in FDC.Conclusion: It was concluded that better reproducibility of results could be achieved with NDDC

Effect of multilevel lower-limb botulinum injections & intensive physical therapy on children with cerebral palsy

Background & objectives: Botulinum toxin is considered as an effective treatment for spasticity in children with cerebral palsy (CP). However, there are only a few long-term studies, and the effects on motor function have been inconclusive. Moreover, due to its high cost and need for intensive post-injection therapy, utility in context of developing nations has not been established. This retrospective study was undertaken to assess the long term effects of botulinum toxin-A with physical therapy in children with CP. Methods: This retrospective study was conducted at a tertiary care centre in India, where a limited supply of botulinum toxin was introduced in the year 2009. It was used in a selective group of patients with CP along with intensive physical therapies. All children who received lower-limb botulinum injections over a 42-month period were analyzed. For evaluation of treatment effect, the measurement at 1st pre-injection assessment and the last measurements, i.e. 12 wk after last injection received by that child were compared. Results: Twenty nine patients (20 males, median age 51 months) received 69 sessions of botulinum toxin injections in the lower limbs over a 42-month period. Thirteen patients were diplegic, 10 were quadriplegic, five were triplegic and one was hemiplegic. There was a significant improvement in pre- and post-injection scores on Observational Gait Scale (right side 7.1±3.6 to 10.7±3.7, left side 6.7±3.5 to 9.9±3.4), Gross Motor Function Measure Scale (47.9±17.7 to 67.6±17.2), Modified Ashworth Scale, passive range of motion and Gross Motor Function Classification System. Most of the patients showed gain in motor milestones as well. Interpretation & conclusions: Our results showed that judicious use of botulinum injections along with intensive physio/occupational therapies could yield good results in children with CP

Structural and functional protection of photoreceptors from MNU-induced retinal degeneration by the X-linked inhibitor of apoptosis

Purpose: To evaluate the neuroprotective effects of adenoassociated virus delivery of XIAP in N-methyl-N-nitrosourea (MNU)-induced retinal degeneration in Sprague-Dawley rats.Methods: Sprague-Dawley rats were injected subretinally with recombinant adenoassociated virus (rAAV) encoding either XIAP or green fluorescent protein (GFP; injection control). Six weeks after injection, the animals received an intraperitoneal injection of MNU, a DNA methylating agent, at a dose of 60 mg/kg. Electroretinograms (ERGs) were recorded at 0, 24, 48 and 72 hours and 1 week after MNU. The rats were killed after the ERG was performed and were perfused with 4% paraformaldehyde. Eyes were then enucleated and embedded for cryosectioning. Eye sections were analyzed by TUNEL and histologic techniques. Real-time PCR and Western analysis were performed to confirm the overexpression of XIAP in injected eyes.Results: Real-time PCR and Western analysis confirmed the overexpression of XIAP in virus-injected eyes in comparison to uninjected control eyes. At 24 hours after MNU injection, fewer cells had undergone apoptosis in the XIAP-treated eyes in comparison with GFP-injected or uninjected eyes. Hematoxylin and eosin staining revealed that the uninjected and GFP-injected photoreceptors were destroyed by 72 hours after injection of MNU, whereas the AAV-XIAP-injected eyes showed structural protection of the photoreceptors at all time points throughout the 1-week sampling period. ERGs showed functional protection up to 1 week after MNU injection in the AAV-XIAP-injected eye, whereas no response was observed in the control eye.Conclusions: The results suggest that XIAP is protective against this potent chemotoxic agent and holds promise as a therapeutic agent in gene therapy approaches to treating retinitis pigmentosa