Résumé
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.
Résumé
Background: Maternal mortality has been the indicator of measurement of maternal health. Over the last decade, identification of severe acute maternal morbidity (SAMM) has emerged as a compliment or alternative to investigation of maternal deaths. A review of causes of SAMM will help to find out the potential problems which in turn will enable women to get the treatment on time. Recent researches have suggested that proper identification of SAMM cases can prove to be a better method to monitor the quality and effectiveness of obstetric care than mortality alone. Although there have been many criteria which have been introduced from time to time to identify these cases, because of vast variation of different level of facilities, these criteria cannot be applied across the regions. WHO has recently come up with certain set of criteria which could be more applicable to low resource settings. Aims & Objective: Present study tried to identify SAMM cases through various criteria and compared the applicability of them in our setup which is resource poor setting catering mainly to a huge rural population. Materials and Methods: It is a prospective study done over a period of one year, from September 2012 to August 2013. All severely morbid pregnant women or who had delivered or aborted within 42days were included. Initial identification of these cases was done on the basis of general criteria and later on other criteria were applied according to the primary obstetric event, clinical features, Lab findings or management provided. A comparison was done amongst all criteria and their individual applicability was checked as per the facility available in our set up. Results: During the study period total 7819 women delivered in the hospital out of which 6498 delivered vaginally and 1321 delivered through caesarian section. Total live births during this period were 5219. The present study found an incidence of severe maternal morbidity/near miss ranging from 5.56 to 40 per 1000 live births. Among 244 women suspected to be SAMM/MNM, 179(73%) met Waterstone’s criteria, 48(20%) met Mantel’s Criteria and 63(26%) met WHO criteria, 20% women met Mantel and Waterstone’s criteria both while 17% met all three criteria. Conclusion: The study of SAMM cases and their identification through suitable criteria can contribute to know its magnitude, as well as to identify most frequent characteristics and clinical conditions which will help to recognize the problems in antenatal services, peripheral health care facilities and referral system. The criteria which are available now cannot be applied uniformly, and need to be tailored to identify more specific criteria according to infrastructure of a particular setting in order to utilize resources effectively.