OPTIMIZATION OF IRBESARTAN TABLET FORMULATION BY 23 FACTORIAL DESIGN

Irbesartan, a widely prescribed anti hypertensive drug belongs to class II under BCS classification and exhibit low and variable oral bioavailability due to its poor aqueous solubility. It needs enhancement in the dissolution rate in its formulation development. Complexation with β-cyclodextrin (βCD) and use of Crospovidone and PVP K 30 are tried for enhancing the dissolution rate of irbesartan in its formulation development. The objective of the present study is optimization of irbesartan tablet formulation employing Crospovidone, βCD and PVP K 30 by 23 Factorial design. Formulation of irbesartan tablets with NLT 85% dissolution in 15 min employing Crospovidone, βCD and PVP K 30 was optimized by 23 Factorial design. Eight irbesartan tablet formulations were prepared using selected combinations of the three Factors as per 23 Factorial designs. Irbesartan tablets were prepared by direct compression method and were evaluated for drug content, hardness, friability, disintegration time and dissolution rate characteristics. The dissolution rate (K1) values were analysed as per ANOVA of 23 Factorial design to find the significance of the individual and combined effects of the three Factors (βCD, Crospovidone and PVP K 30) involved on the dissolution rate of irbesartan tablets formulated. The individual and combined effects of βCD, Crospovidone and PVP K 30 on the dissolution rate (K1) of irbesartan tablets are highly significant (P<0.01). Irbesartan tablet formulation (PFac), disintegrated rapidly with in 1 min and gave very rapid dissolution of irbesartan,100% in 15 min. Higher levels of βCD and lower levels of Crospovidone gave low dissolution rates of irbesartan tablets. The increasing order of dissolution rate (K1) observed with various formulations was CFac> CFa>CFab>CFabc> CF1> CFbc> CFb> CFc. The polynomial equation describing the relationship between the response i. e. percent drug dissolved in 15 min (Y) and the levels of Crospovidone (X1),βCD (X2) and PVP K 30 (X3) based on the observed results is Y = 58.57+34.54 (X1) - 1.89(X2) – 3.60 (X1 X2) -1.82 (X3) +1.50 (X1 X3) + 3.13 (X2 X3) - 4.87 (X1 X2 X3). Based on the above polynomial equation, the optimized irbesartan tablet formulation with NLT 85% dissolution in 15 min could be formulated employing Crospovidone at 27.70% of drug content, βCD at 1:4 ratio of drug: βCD and PVP K 30 at 1% of drug content. The optimized irbesartan tablet formulation gave 86.18 % dissolution in 15 min fulfilling the target dissolution set. The dissolution profile of the optimized Irbesartan tablet formulation was similar to that of commercial brand (IROVEL-150). Hence the formulation of irbesartan tablets with NLT 85% dissolution in 15 min could be optimized by 23 Factorial design

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass