M. Sreenivasa Reddy

Preparation and evaluation of minoxidil gels for topical application in alopecia

In the present study four minoxidil gels were prepared using carbopol, hydroxypropyl cellulose, hydroxypropyl methylcellulose and combination of hydroxypropyl cellulose, hydroxypropyl methylcellulose for the treatment of alopecia. The gels were evaluated for drug content, viscosity determination, in vitro permeation (across dialysis membrane and mouse skin), skin irritation and stability at 4, 25 and 37° tests. The drug content of the gels was found to range from 96.40±0.57 to 98.10±0.32%. The viscosity of the gels ranged between 13,780±100 and 24,950±150 cps. The drug permeation across dialysis membrane from all the formulations at the end of 24 h was almost same and ranged between 92.05±1.52 and 93.52±1.95%. Although the difference is insignificant, the percentage release of drug was found to increase in the following order of the polymer composition: HPC>Carbopol>HPMC>HPMC+HPC. All the gel formulations released almost similar amounts of drug (90.05±1.92 to 91.56±1.65%) across the mouse skin; but the cumulative amount of drug permeated across dialysis membrane was more than that of the mouse skin. The marketed topical solution was found to diffuse almost 100% of drug across dialysis membrane and mouse skin at the end of 12 h. As supported by Higuchis equation, the drug release mechanism from all the gels was found to be diffusion dominated. The prepared gels did not produce any dermatological reactions and were well tolerated by the mice. The gels were found to be stable with respect to viscosity, drug content and physical appearance at all temperature conditions for 3 months.

IRREGULAR SOLUTION BEHAVIOUR OF PARACETAMOL IN BINARY SOLVENTS

Abstract The irregular solution behaviour of paracetamol was observed in two solvent systems: ethyl acetate-methanol; water and normal alcohols. The extended Hildebrand solubility approach was used to process the solubility data on paracetamol. The solubility parameter of paracetamol was determined from different methods of data analysis and found to be approx. 13.40 H. The parameters W and (log γ 2 )/ A were regressed against a polynomial of δ 1 of the binary mixture. The expressions allowed calculation of the mole fraction solubility of paracetamol in polar solvents. The expression for W regression was satisfactory for the determination of the solubility of paracetamol in methanol, ethanol and their mixtures, but deviated in the case of butanol and propanol.

Full factorial design for optimization, development and validation of HPLC method to determine valsartan in nanoparticles.

High performance liquid chromatographic method was optimized, developed and validated as per the ICH guidelines. In this study the 20 mM ammonium formate and acetonitrile in the 57:43 ratio were used as mobile phase for the analysis of valsartan. Full factorial design was used to optimize the effect of variable factors. The responses were peak area, tailing factor and number of theoretical plates. The quadratic effect of flow rate and wavelength individually as well as in interaction were most significant (p < 0.0001 and p < 0.0086, respectively) on peak area; the quadratic effect of pH of buffer was also most significant effect (p < 0.0001) on tailing factor (5%) whereas the quadratic effect of flow rate and wavelength individually was significant (p = 0.0006 and p = 0.0265, respectively) on the number of theoretical plates. The high-performance liquid chromatographic separation was performed at the flow rate 1.0 min/mL, UV detector wavelength 250 nm and pH of the buffer 3.0 as optimized parameters using design of experiments. The retention time values of valsartan were found to be 10.177 min. Percent recovery in terms of accuracy for the prepared valsartan nanoparticles was found in the range of 98.57–100.27%.

Methotrexate-loaded Biodegradable Nanoparticles:Preparation, Characterization and Evaluation of its Cytotoxic Potential Against U-343 MGa Human Neuronal Glioblastoma Cells

Nanoparticles represent one of the attractive alternatives in the effective treatment of cancer chemotherapy. In the present work, formulation and development of a novel methotrexate (MTX)-loaded biodegradable nanoparticles using poly(D,L-lactide-co-glycolide) (PLGA) was carried out. The prepared nanoparticles were evaluated for physicochemical properties such as particle size, zeta potential, release studies, etc and also evaluated for its in vitro cytotoxic potential against U-343 MGa human neuronal glioblastoma cells. Particle size of optimized formulation was < 200 nm. There was a considerable decrease in cell viability and enhancement in cytotoxic activity of MTX-loaded nanoparticles compared to MTX alone when tested against U-343 MGa human neuronal glioblastoma cells.

Osmotically controlled pulsatile release capsule of montelukast sodium for chronotherapy: Statistical optimization, in vitro and in vivo evaluation

Abstract The purpose of present study was to design, optimize and evaluate osmotically controlled pulsatile release capsule (PRC) of montelukast sodium (MKS) for the prevention of episodic attack of asthma in early morning and associated allergic rhinitis. Assembly of the capsular systems consisted of push, active and plug tablet arranged from bottom to top in hard gelatin capsule. The capsule system was coated with a semi-permeable membrane of cellulose acetate and drilled towards plug side in cap. A three-factor, three-level central composite design (CCD) with α = 1 was introduced to execute the experiments and quadratic polynomial model was generated to predict and assess the independent variables with respect to the dependent variables. The composition of optimal formulation was determined as weight of push tablet 138 mg (coded value: +0.59), plug tablet 60 mg (coded value: +0.49) and coating weight gain of 8.4 mg (coded value: −0.82). The results showed that the optimal formulation of PRCs had lag time of 4.5 h, release at 6 and 12 h are 61.95% and 96.29%, respectively. The X-ray radiographic imaging study was carried out to monitor the in vivo behavior of developed barium sulfate-loaded PRCs in rabbits under fasting conditions. In vivo pharmacokinetic study revealed Tmax of 2 h for marketed tablets; however 7 h for PRCs with initial lag time of 4 h. Thus designed capsular system may be helpful for patients with episodic attack of asthma in early morning and associated allergic rhinitis.

Formulation and characterisation of nanosuspensions of BCS class II and IV drugs by combinative method

Drug nanocrystals are known to increase the solubility of Biopharmaceutics Classification System (BCS) class II and IV drugs. SmartCrystals are the second generation nanocrystals with particle size of less than 100 nm and increased the stability and solubility of drug and drug product. The combinative methods adopted for the preparation of SmartCrystals are reported to shorten the processing time to reduce the particle size of the drug. This study was carried out with the aim to prepare nanosuspensions of aprepitant and ibuprofen using two pretreatment methods, precipitation and ball milling in a combination of high-pressure homogenisation (HPH). Ball milling and precipitation resulted in nanosuspensions having a particle size less than 1 µ, which were subjected to high HPH. HPH further led to a reduction in the particle size. However, the precipitation method failed to reduce the size of ibuprofen particles to 1 µ.

Formulation, characterization and In vivo evaluation of self-nanoemulsifying drug delivery system for oral delivery of valsartan

Valsartan is an effective, highly selective and orally active antihypertensive exhibiting low aqueous solubility and poor dissolution that limit its absorption resulting in low bioavailability. The objective of the present study was to prepare and characterize selfnanoemulsifying drug delivery system (SNEDDS) of Valsartan and evaluate their performance in animal models. SNEDDS was prepared by the spontaneous emulsification method. Saturation solubility of the drug was studied in various oils, surfactants and co-surfactants. The formulations were characterized for droplet size, shape, DSC, FTIR, in vitro drug release and for pharmacokinetic studies in Wistar rats. SNEDDS were prepared using triacetin and castor oil as oil phase, Tween 80 as surfactant and PEG 600 as co-surfactant. The globule size was 139.29 ± 10.5 nm for triacetin SNEDDS and 142.6 ± 18.6 nm for castor oil SNEDDS when diluted with 500-fold volume of the Milli-Q water. TEM images confirmed the uniform shape and nano size of the system. The formulations were stable on storage at accelerated conditions. The SNEDDS significantly increased the Cmax and area under the curve (AUC) compared to that of the pure Valsartan. Thus SNEDDS can be effectively used to improve the oral bioavailability of Valsartan.

Bioactive PLGA–curcumin microparticle-embedded chitosan scaffold: in vitro and in vivo evaluation

Abstract Wound healing is a complex process affected by several factors. In the present work, novel biocompatible PLGA–curcumin microparticle-embedded chitosan scaffold was fabricated for wound-healing application. Process variables involved in the preparation of microparticles were optimized using design of experiment. Scanning electron microscopy (SEM) confirmed the porous nature of scaffold with embedded microparticles. A maximum release of 14% of the encapsulated curcumin was observed at 12th hour. Modified tube dilution method showed that scaffold significantly (p < 0.05) reduced multiplication of Staphylococcus aureus. More than 50% of the excised wound in rats healed in 4 days with an epithilization period of 18 days.

Pharmaceutical applications of radio-frequency identification

Radio-frequency identification (RFID) is a small electronic device that utilizes the radio waves for the purpose of security, personnel identification, surveillance, medical identification, patient history, library automation, baggage application, toll collection, file tracking, electronic payment, etc. Three types of RFID tags namely, active, passive, and semi-passive RFID tags, are currently available. The basic components of RFID system are RFID transponder, antenna, and transceiver. This review mainly focuses on the various applications of RFIDs in the pharmaceutical sector. RFID has potential applicability in pharmaceutical and healthcare sectors such as product tracking and inventory control, limiting the Bullwhip effect, supply chain management, maintenance of dyes and punches, preclinical study, identification of patients and hospital staff, avoidance of medication errors, etc., which have been discussed in detail. Besides having innumerable applications, RFID technology is in its early stages in pharmaceutical systems and hence its potential is required to be explored more in practical. The RFID systems are expensive which makes the adaptability of this system very difficult. Hence the development of low cost RFIDs is a big challenge at present and more research activities are required in this direction.

Development of Fluconazole Suppositories for the Treatment of Candida Infection of Genitourinary Tract

Background: Vulvovaginal candidiasis is a communal problem in virtually all the women which is caused by Candida albicans. Objective: Aim of the present study was to prepare and characterize vaginal suppositories of fluconazole for the treatment of vulvovaginal candidiasis. Methods: Fluconazole suppositories were prepared using water soluble and fatty bases. Bases and their proportions used were selected in such a way that they have flexibility in storage conditions unlike conventional suppositories. Suppositories were prepared and examined for physical characteristics and in vitro release studies. Results: Present study showed ultimate results with respect to the physical characteristics of suppositories and in vitro drug release studies. In vitro drug release from the prepared suppositories was in the following order FVS 3 (100.00 ± 3.7% in 1.0 h) > FVS 1 (86.29 ± 4.9% in 12.0 h) > FVS 2 (80.47 ± 2.4% in 12.0 h) > FVS 5 (22.51 ± 0.42% in 24.0 h) > FVS 4 (18.09 ± 1.31% in 24.0 h). These drug release results are supported by the disintegration time of suppositories. Lesser the disintegration time faster the drug release. Conclusion: Study concludes that it may be fruitful to explore the in vivo activities of suppositories prepared with the combination of agar and HPMC as it showed around 80% drug release over 12.0 h. Represented combination may also be more effective for the treatment of vulvovaginal candidiasis.