Co-processing of cefuroxime axetil by spray drying technique for improving compressibility and flow property.

The aim of the present investigation was to improve the compressibility and flow property of cefuroxime axetil by co-processing it with mannitol and chitosan chlorhydrate using spray drying method. 32 full factorial design, having inlet air temperature and mannitol: chitosan chlorhydrate ratio as independent variables was used for the optimization. Statistical analysis of obtained results revealed that both independent variables had significant effect on response variables (p value < .05). Evaluation of dependent variables suggested, excellent to good flow properties (angle of repose, Carr's index, and Hausner's ratio) for all prepared batches. Desirability function was used for the selection of the optimized batch which was evaluated for Kawakita's equation, Heckel's plot to assess compression behavior of co-processed product under applied pressure. Result of this analysis revealed that the optimized batch product had better compressibility than physical mixture. The tablets prepared by directly compressing spray-dried product, exhibited excellent tensile strength acceptable friability (<1%) and similar release profile when compared with marketed formulation (Similarity factor 89.24 and dissimilarity factor 1.79). So the results of the present investigation concluded that cefuroxime axetil was successfully co-processed with above mentioned excipients by using spray drying method to make it directly compressible.

Development and Characterization of Multifunctional Directly Compressible Co-processed Excipient by Spray Drying Method.

The present investigation was carried out to develop and characterize a multifunctional co-processed excipient for improving the compressibility of poorly compressible drugs. Etodolac was used as a model drug. Microcrystalline cellulose (MCC), lactose monohydrate (lactose), and StarCap 1500 (StarCap) were selected as components of the co-processed excipient. The spray drying method was used for co-processing of excipients. D-optimal mixture design was applied to optimize the proportion of component excipients. Statistical analysis of the D-optimal mixture design revealed that all response variables were significantly affected by the independent variables (p value < 0.05). Optimized composition was obtained from the desirability function. The optimized composition of the co-processed excipient was found to be 30% MCC, 25% lactose, and 45% StarCap. This optimized batch was evaluated for flow properties, compressibility parameters such as Kawakita's and Kuno's equation and Heckel's equation, and dilution potential. Evaluation parameters for flow properties (angle of repose, Carr's index, and Hausner's ratio) suggested excellent flow character. The parameters of Kawakita's and Kuno's equation and Heckel's equation suggested improvement in the compressibility of the model drug. Dilution potential was found to be 40%, and based on that, tablets of the model drug were formulated and evaluated for general evaluation parameters of tablets. All the parameters were found to be within the acceptance criteria which concluded that the multifunctional directly compressible co-processed excipient was prepared successfully that improved the compressibility of the poorly compressible model drug etodolac along with spray drying as an efficient method for the preparation of co-processed excipient.

Microemulgel of Voriconazole: an Unfathomable Protection to Counter Fungal Contagiousness.

BACKGROUND: Fluconazole and ketoconazole both have poor minimum inhibitory concentration than voriconazole. Voriconazole had serious side effects in oral and intravenous doses. It has poor water solubility. The objective of the study was to prepare and optimize microemulgel of voriconazole for topical delivery. AIM: Formulation, development, and evaluation of voriconazole microemulgel for topical delivery. METHODS: Oil and emulsifi ers selected were on the basis of equilibrium solubility study and emulsification property respectively. The pseudo-ternary plot and constrained simplex lattice design were applied for preparation of microemulsions. Microemulsions were subjected to micelle size, zeta potential, polydispersity index, and in vitro study. They were optimized by Design-Expert® 9.0.3.1 software. Formulation, development, evaluation and optimization of microemulgel were carried out. Microbial assay of an optimized batch of microemulgel was performed. RESULTS: Solubility of voriconazole in Parker Neem® oil was 7.51±0.14 mg/g. Acrysol™K-150: PEG-400 in 4:1 ratio had the highest area for microemulsion. 59.2% Acrysol™K-150, 14.8% PEG-400, 11% Parker Neem® oil, 15% rose water, and 1% voriconazole as an optimized batch of microemulsion was selected for preparation of microemulgel. Carbomer 934P found a good gelling agent in 0-2% w/w concentration. An optimized batch of microemulgel had 0.974 desirability value. An optimized batch of microemulgel and Nizral® cream had 37.32±0.63% and 26.45±0.63% zones of inhibition. CONCLUSION: Topical antifungal treatment was successfully achieved with voriconazole microemulgel.

Design, Optimization, and Evaluation of Lurasidone Hydrochloride Nanocrystals.

The present investigation was carried out to design, optimize, and evaluate lurasidone hydrochloride nanocrystals for improving its solubility and dissolution characteristics. Nanocrystals were prepared by media milling technique using zirconium oxide beads with 0.1 mm diameter. Various stabilizers, viz. poloxamer 188, PVP K30, SLS, HPMC E15, and PVP S 630 D, were evaluated to stabilize the nanocrystals. The Pareto chart obtained through Plackett-Burman screening design revealed that HPMC E 15 showed the highest standardized effect (p value <0.05) on percent dissolution efficiency at 2 min. In subsequent studies, a 3(2) factorial design was employed to quantify the effect of two independent variables, namely amount of stabilizer and milling time on predetermined response variables mean particle size, saturation solubility, and percent dissolution efficiency at 2 min. Statistical analysis of the factorial design revealed that all predetermined response variables were significantly dependent (p value <0.05) on the independent variables. The observed response of the optimized batch prepared as per the desirability function was in close agreement with predicted response, and mathematical model generated was validated. The optimized batch was lyophilized, and X-ray powder diffraction studies indicated that there was no substantial change in crystallinity of the drug. The optimized formulation showed mean particle size of 228 nm and released almost all the drug within first 5 min. Since the crystallinity of the drug is maintained, improvement in saturation solubility and dissolution efficiency could be attributed to decrease in mean particle size of the drug.

Development and optimization of press coated tablets of release engineered valsartan for pulsatile delivery.

The present work is aimed to develop and optimize pulsatile delivery during dissolution of an improved formulation of valsartan to coordinate the drug release with circadian rhythm. Preliminary studies suggested that ß cyclodextrin could improve the solubility of valsartan and showed AL type solubility curve. A 1:1 stoichiometric ratio of valsartan to ß cyclodextrin was revealed from phase solubility studies and Job's plot. The prepared complex showed significantly better dissolution efficiency (p < 0.05) compared to pure drug, which could be due to the formation of inclusion complex as revealed from FTIR and DSC studies. Continuous dissolution-absorption studies revealed that absorption of drug from valsartan ß cyclodextrin complex was significantly higher (p < 0.05) compared to pure drug, in second part press-coated tablets of valsartan ß cyclodextrin complex were subsequently prepared and application of the Plackett-Burman screening design revealed that HPMC K4M and EC showed significant effect on lag time. A 3(2) full factorial design was used to measure the response of HPMC K4M and EC on lag time and time taken for 90% drug release (T90). The optimized batch prepared according to the levels obtained from the desirability function had a lag time of 6 h and consisted of HPMC K4M:ethylcellulose in a 1:1.5 ratio with 180 mg of coating and revealed a close agreement between observed and predicted value (R(2 )= 0.9694).

Lipids Fortified Nano Phytopharmaceuticals: A Breakthrough Approach in Delivering Bio-actives for Improved Therapeutic Efficacy.

Phytopharmaceuticals, derived from natural sources, manifest tremendous potential for therapeutic applications. Nevertheless, effective delivery of these bio-actives presents significant challenges. A breakthrough in fortifying phytopharmaceuticals within phosphatidylcholine is a promising remedy to overcome solubility, permeability, and other related drawbacks. This intrinsic lipid, which is obtained from both natural and synthetic sources, confers numerous benefits, encompassing heightened solubility, augmented bioavailability, and enhanced stability. The conjugation of phytopharmaceuticals with phosphatidylcholine enables improved dermal permeation, absorption, targeted distribution, and the possibility of synergistic results, eventually improving therapeutic efficacy. Additionally, the use of phytopharmaceuticals enriched with phosphatidylcholine presents a promising route for overcoming the limitations imposed by conventional delivery techniques, encouraging more effective treatments. The review provides a thorough analysis of phosphatidylcholine- incorporated phytopharmaceuticals as nanomedicine with variables that significantly affect their therapeutic efficacy. Moreover, the review elaborates on how phosphatidylcholine improves solubility, permeability, and tissue distribution and boosts the potential of phytopharmaceuticals. Further, the review underscores the significance of nano-formulation strategies, analytical methodologies, and forthcoming prospects to propel this field forward. Furthermore, the review emphasizes the potential inherent in this innovative approach while highlighting the importance of additional research endeavors and collaborative initiatives to unlock the therapeutic benefits of phosphatidylcholinefortified phytopharmaceuticals, enhancing patient well-being.

Development and Optimization of Inhalable Levofloxacin Nanoparticles for The Treatment of Tuberculosis.

BACKGROUND: Levofloxacin has been recommended by the WHO for the treatment of pulmonary tuberculosis and inhalable delivery of levofloxacin can be advantageous over conventional delivery. OBJECTIVE: This study aimed to develop and optimize inhalable levofloxacin Loaded Chitosan Nanoparticles (LCN). The objective was to achieve the mean particle size of LCN less than 300nm, sustain the drug release up to 24 h, and achieve MMAD of LCN of less than 5µm. METHODS: LCN were prepared by ionic gelation of chitosan with sodium tripolyphosphate (STPP) and subsequent lyophilization. A Plackett Burman screening design, 32 full factorial design, and overlay plots were sequentially employed to optimize the formulation. The mean particle size, % entrapment efficiency, in vitro drug release, and minimum inhibitory concentration were all evaluated. RESULTS: The Pareto chart from the Placket Burman screening design revealed that the concentrations of chitosan and STPP was found to be significant (p < 0.05). Further analysis by 32 full factorial design revealed that F-ratio for each model generated was found to be greater than the theoretical value (p < 0.05), confirming the significance of each model. CONCLUSION: The optimized formulation showed a mean particle size of 171.5 nm, sustained the drug release up to 24 h in simulated lung fluid, and revealed MMAD of 3.18 µm, which can confirm delivery of the drug to the deep lung region. However, further in vivo studies are required to design a suitable dosage regimen and establish the fate of nanoparticles for safe and efficacious delivery of the drug.

Lymphatic filariasis vaccine development: neglected for how long?

INTRODUCTION: Lymphatic filariasis (LF), also known as elephantiasis, has been recognized by the world health organization and the centers for disease control and prevention as one of the neglected tropical diseases. The huge prevalence and risk of manifestation to date reflect the poor management of this disease. The disease poses vast public health and socio-economic burdens and generates a dire need for the development of a prophylactic solution for mass administration. AREAS COVERED: Vaccination has been a sought-out strategy for dealing with ever-evolving infectious diseases and can be duly tuned to become a cost effective means of disease control and eventual eradication. In this review, we highlight the epidemiology of LF with the current diagnosis and treatment modules. The need for the development of a potential vaccine candidates, and challenges are discussed. The evidence presented in this review aims to enlighten the readers regarding the essential factors governing LF and its management using prophylactic measures. EXPERT OPINION: The complex nature of filarial parasites is evident from the absence of a single vaccine for LF. The development and selection of an appropriate preclinical model and its translation into clinical practice is deemed to be a major task needing in-depth evaluation to formulate an effective vaccine. Explorations of the existing vaccine platforms would serve to be an apt strategy in this direction.

Formulation and optimization of microsponge-loaded emulgel to improve the transdermal application of acyclovir-a DOE based approach.

The cutaneous penetration of acyclovir from the conventional topical formulations such as cream and ointments is poor due to low water solubility and low octanol buffer partition coefficient of the drug. The present investigation was aimed to prepare acyclovir-loaded microsponge-based emulgel to improve its topical delivery. The microsponges were prepared by the quasi-emulsion diffusion method. The central composite design was employed to investigate the effect of changes in various formulation and process parameters on critical product attributes. Homogenization speed (X1), drug/polymer ratio (X2), and concentration of PVA (X3) were selected as independent variables while particle size,b% yield, % drug loading efficiency, % entrapment efficiency, the drug released at 0.25 h and 6 h were selected as response variables. The regression analysis proved a significant effect of all the independent variables on the dependent variables (p < 0.05). All the designed batches released more than 40% drug in less than 1 h and were also able to sustain the drug release for more than 6 h. Based on the solution suggested by the software, the optimized batch was prepared with 1000-rpm homogenization speed, 1.6:1 drug/polymer ratio, and 0.088% of PVA. The optimized microsponge-loaded emulgel had acceptable viscosity (10,897 to 12,416 centipoise), spreadability (32.5 to 36.57 g × cm/s), pH (between 6 and 7), and drug content (93 to 95%). The results of the ex vivo permeation study proved significant improvement in drug permeation from optimized microsponge-loaded emulgel compared to the marketed formulation (f2 < 50).

Pharmacokinetics and in vivo distribution of optimized PLGA nanoparticles for pulmonary delivery of levofloxacin.

OBJECTIVES: The aim of this study was to develop and optimize levofloxacin loaded PLGA nanoparticles (LN) for pulmonary delivery employing screening and experimental design and evaluate their in-vitro and in-vivo performance. The objective was to achieve Mass Median Aerodynamic Diameter (MMAD) of LN of less than 5µm, sustain the drug release up to 120 h and a higher AUC/MIC at the site of action. METHODS: LN were prepared by modified emulsion solvent evaporation technique employing high speed homogenization, probe sonication and subsequent lyophilization. KEY FINDINGS: The Pareto chart from Placket Burman screening design revealed that homogenization speed and amount of PLGA were found to be significant (P < 0.05). Further analysis by 3 full-factorial design revealed that F-ratio was found to be far greater than the theoretical value (P < 0.05) for each regression model. CONCLUSION: The optimized formulation with desirability value 0.9612 showed mean particle size of 146 nm, MMAD of 4.40 µm and sustained the drug release up to 120 h in simulated lung fluid. Augmentation in Cmax (1.71-fold), AUC 0-∞ (5.46-fold), Mean Residence Time (6.64-fold) and AUC/MIC (6.21-fold) of LN through pulmonary route was found to significantly higher (P < 0.05) than levofloxacin (p. o.).