Glyceryl behenate-based solid lipid nanoparticles as a carrier of haloperidol for nose to brain delivery: formulation development, in-vitro, and in-vivo evaluation

Abstract This study was aimed to develop the haloperidol (HPL) loaded solid lipid nanoparticles (SLNs) for brain targeting through the intranasal route. SLNs were fabricated by the emulsification diffusion technique using glyceryl behenate as lipid and tween 80 as a surfactant. SLNs were evaluated for particle size, zeta potential, structure, entrapment efficiency, solid state characterization by differential scanning calorimetry (DSC), and in-vitro release. In-vivo biological evaluation was performed on albino Wistar rats for the determination of pharmacokinetic as well as brain targeting parameters. Particle size, PDI, zeta potential, and entrapment efficiency of optimized formulation (HPL-SLNs 6) were found to be 103±09 nm, 0.190±0.029, -23.5±1.07 mV, and 79.46±1.97% respectively. In-vitro drug release studies exhibited that 87.21± 3.63% of the entrapped drug was released from the SLNs within 24 h. DSC curves confirmed that during entrapment in SLNs, the drug was solubilized in the lipid matrix and converted into the amorphous form. Enhanced HPL targeting to the brain was observed from HPL-SLNs as compared to HPL-Sol when administered intranasally. The value of AUC 0-∞ in the brain for HPL-SLNs i.n. was found to be nearly 2.7 times higher than that of HPL-Sol i.v., whereas 3.66 times superior to HPL-Sol administered i.n. Stability studies revealed that the formulation remains unchanged when stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months. Finally, it could be concluded that SLN is a suitable carrier for HPL with enhanced brain targeting through i.n administration, as compared to the HPL-Sol, administered i.n. and i.v.

Development of a new HPLC method for in vitro and in vivo studies of haloperidol in solid lipid nanoparticles

ABSTRACT A simple and sensitive HPLC method was developed and validated for the quantification of haloperidol in solid lipid nanoparticles (SLNs). The developed method was used for detection of shelf life of haloperidol in SLNs. Calibration curve of haloperidol was also constructed in rat plasma using loratidine as internal standard. In vivo studies were performed on rats and concentration of haloperidol in brain and blood was measured for the determination of various pharmacokinetic and hence brain targeting parameters. Chromatogram separation was achieved using C18 column as stationary phase. The mobile phase consisted of 100 mM/L potassium dihydrogen phosphate-acetonitrile-TEA (10:90:0.1, v/v/v) and the pH was adjusted with o-phosphoric acid to 3.5. Flow rate of mobile phase was 2 mL/minute and eluents were monitored at 230 nm using UV/VIS detector. The method was validated for linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). Linearity for haloperidol was in the range of 1-16 µg/mL. The value of LOD and LOQ was found to be 0.045 and 0.135 μg/mL respectively. The shelf life of SLNs formulation was found to be 2.31 years at 4 oC. Various parameters like drug targeting index (DTI), drug targeting efficiency (DTE) and nose-to-brain direct transport (DTP) were determined for HP-SLNs & HP-Sol administered intranasally to evaluate the extent of nose-to-brain delivery. The value of DTI, DTE and DTP for HP-SLNs was found to be 23.62, 2362.43 % and 95.77% while for HP-Sol, values were 11.28, 1128.61 % and 91.14 % respectively.

Sustained release solid dispersion of Metoclopramide HCL: formulation, evaluation and pharmacokinetic studies.

In recent years oral controlled delivery systems have gained increased importance and interest since it is necessary to improve the systemic absorption of the drugs and patient compliance. In addition, controlled delivery systems maintain uniform drug levels, reduce dose and hence dose related side effect, and increase the safety margin. The objective of present work was prepared sustained release solid dispersion of Metoclopramide HCl by solvent evaporation method. Several polymers like combination of Eudragit RSPO - Eudragit RLPO and Guargum-Egg albumin as synthetic and natural polymers respectively were used. Several parameters like Solubility, Partition coefficient, Drug content, Percent drug release, Bulk density, Tapped density and Carr’s index were evaluated and all parameters were found to be in acceptable range. The results of XRD and SEM analysis were showed that the drug was converted into a solid dispersion. The In vivo studies were performed on Albino Wistar rats and various pharmacokinetics parameters were determined. The whole study was showed that the solid dispersion of Metoclopramide HCl sustained the release rate of drug for a prolong period of time at least 12 hrs and shows to increase the bioavailability and simultaneously decrease the dosing interval as well as dosing amount. The formulation minimizes the blood level oscillations, dose related adverse effects and cost and ultimately improve the patient compliance and drug efficiency.

Development and Validation of UV Spectrophotometric Method for the Estimation of Haloperidol.

Aims: The aim of the present work was to develop and validate a sensitive, simple, accurate, precise & cost effective UV spectrophotometric method for the estimation of haloperidol in prepared pharmaceutical formulations of solid lipid nanoparticles. Methodology: The different analytical performance parameters such as linearity, range, precision, accuracy, limit of detection (LOD) and limit of quantification (LOQ) were determined according to International Conference on Harmonization (ICH) Q2 (R1) guidelines. The study was performed in phosphate buffer of pH 7.4. Results: The peak (λmax) of haloperidol appeared at a wavelength of 247.5 nm in phosphate buffer (pH 7.4). Beer-Lambert’s law was obeyed in the concentration range of 2–20 μg/ml with correlation coefficient (R2) 0.9994. Conclusion: The results of the study demonstrated that the developed procedure was accurate, precise and reproducible, while being simple, cheap and less time consuming. Therefore, this method can be suitably applied for the estimation of haloperidol in prepared solid lipid nanoparticles.

Formulation and evaluation of Paclitaxel loaded PSA-PEG nanoparticles.

The main objective of this study was to prepare and evaluate PSA-PEG nanoparticles containing paclitaxel as a model drug by nanoprecipitation method. The influence of different experimental parameters on the particles size, entrapment efficiency, percent drug released etc was evaluated. SEM indicated that nanoparticles have discrete spherical structure without aggregation. The average particle size was found to be 123 -405 nm. The particle size of nanoparticles increases gradually with PSA-PEG polymer concentration. The drug content of nanoparticles also increases with increasing polymer concentration up to particular value. The in-vitro drug release behavior from all drug loaded batches was found to be zero order and provided sustained release over a period of 24 hours. Nanoparticles were stored at different temperatures and humidity as per ICH guidelines to check the stability.

Orally disintegrating tablets : formulation, preparation techniques and evaluation.

Oral delivery is currently the gold standard in the pharmaceutical industry where it is regarded as the safest, most convenient and most economical method of drug delivery having the highest patient compliance. Formulation of a convenient dosage form for oral administration, by considering swallowing difficulty especially in case of geriatric and pediatric patient leads to poor patient compliance. To troubleshoot such problems a new dosage form known as orally disintegrating tablet (ODT), has been developed which rapidly disintegrate & dissolve in saliva and then easily swallowed without need of water which is a major benefit over conventional dosage form. In addition, patients suffering from dysphasia, motion sickness, repeated emesis and mental disorders prefer such preparation because they cannot swallow large quantity of water. Further, drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated in such type of dosage form. The popularity and usefulness of the formulation resulted in development of several ODT technologies for preparation. The current article is focused on ideal characteristics, advantages and disadvantages, formulation aspects, formulation technologies, evaluation of products and future potential. Various marketed preparations along with numerous scientific advancements made so far in this avenue have also been discussed.

Iontophoretic drug delivery: History and applications.

The goal of delivery system is to get optimal therapeutic management. But, it still remains a challenge in the field of pharmaceuticals for delivery of ionic species and some non ionic. Several transdermal approaches have been used and recently there has been a great attention in using iontophoretic technique for the transdermal drug delivery of medications, both ionic and non ionic. This technique of facilitated movement of ions across a membrane under the influence of an externally applied electric potential difference is one of the most promising physical skin penetrations enhancing method. The payback of using iontophoretic technique includes improved systemic bioavailability ensuing from bypassing the first metabolism. Variables due to oral administration, such as pH, the presence of food or enzymes and transit times can all be eliminated. This article is an overview of the history of iontophoresis, mechanism, principles and factors influencing iontophoresis and its application for various dermatological conditions.