Enteric coated HPMC capsules plugged with 5-FU loaded microsponges: a potential approach for treatment of colon cancer

The work was aimed at developing novel enteric coated HPMC capsules (ECHC) plugged with 5 Florouracil (5-FU) loaded Microsponges in combination with calcium pectinate beads. Modified quasi-emulsion solvent diffusion method was used to formulate microsponges based on 32 factorial design and the effects of independent variables (volume of organic solvent and Eudragit RS100 content) on the dependent variables (Particle size, %EE & % CDR) were determined. The optimized microsponges (F4) were characterized by SEM, PXRD, TGA and were plugged along with calcium pectinate beads in HPMC capsules and the HPMC capsules were further coated with enteric polymer Eudragit L 100 (Ed-L100) and/ or Eudrgit S 100 (Ed-S 100) in different proportions. In vitro release study of ECHC was performed in various release media sequentially SGF for 2 h, followed by SIF for the next 6 h and then in SCF (in the presence and absence of pectinase enzyme for further 16 h). Drug release was retarded on coating with EdS-100 in comparison to blend of EdS-100: EdL-100 coating. The percentage of 5-FU released at the end of 24 h from ECHC 3 was 97.83 ± 0.12% in the presence of pectinase whereas in control study it was 40.08 ± 0.02% drug. The optimized formulation was subjected to in vivo Roentgenographic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon targeted capsules. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to 5-FU aqueous solutions. Thus, enteric coated HPMC capsules plugged with 5-FU loaded microsponges and calcium pectinate beads proved to be promising dosage form for colon targeted drug delivery to treat colorectal cancer.

O trabalho teve como objetivo o desenvolvimento de novas cápsulas com revestimento entérico HPMC (ECHC) conectadas com microesponjas carregadas com fluoruracila (5-FU) em combinação com grânuos de pectinato de cálcio. O método de difusão de solvente modificado quasi-emulsão foi usado para formular microesponjas com base no planejamento fatorial 32 e determinaram-se os efeitos das variáveis independentes (volume de solvente orgânico e conteúdo Eudragit RS100) sobre as variáveis dependentes (tamanho de partícula, EE% e % CDR). As microesponjas otimizadas (F4) foram caracterizadas por SEM, PXRD, TGA e ligadas aos grânulos de pectinato de cálcio em cápsulas de HPMC e estas foram, ainda, revestidas com polímero entérico Eudragit L 100 (Ed-L100) e/ou Eudrgit S 100 (Ed S 100) em diferentes proporções. No estudo de liberação in vitro de ECHC foi realizada em vários meios de liberação sequencial SGF durante 2 h, seguido de SIF para as próximas 6 h, e, em seguida, em SCF (na presença e na ausência de enzima pectinase por mais 16 h). A liberação do fármaco foi retardada em revestimento com a EDS-100, em comparação com mistura de EDS-100: EDL-100, de revestimento. O percentual de 5-FU liberado de ECHC 3 ao final de 24 h foi 97,83 ± 0,12% em presença de pectinase, enquanto que para o controle foi de 40,08 ± 0,02% do fármaco. A formulação otimizada foi submetida a estudos Roentgenográficos in vivo, em coelhos brancos Nova Zelândia, para analisar o comportamento das cápsulas desenvolvidas direcionadas ao cólon. Os estudos de farmacocinética em coelhos brancos da Nova Zelândia foram conduzidos para determinar a extensão da exposição sistêmica propiciada pela formulação desenvolvida, em comparação com solução aquosa de 5-FU. Assim, cápsulas entéricas de HPMC revestidas e conectadas com microesponjas carregadas com 5-FU e grânulos de pectinato de cálcio se mostraram promissoras como formulação para liberação do fármaco no cólon no tratamento do câncer colorretal.

Advances in nasal trans-mucosal drug delivery.

Transmucosal nasal delivery is a promising drug delivery option where common drug administrations, such as intravenous, intramuscular, or oral are inapplicable. Recently, it has been shown that many drugs have better bioavailability by nasal route than the oral route. This has been attributed to rich vasculature and a highly permeable structure of the nasal mucosa coupled with avoidance of hepatic first-pass elimination, gut wall metabolism and/or destruction in the gastrointestinal tract. The physiology of the nose presents obstacles, but offers a promising route for non-invasive systemic delivery of numerous therapies and debatably drug delivery route to the brain. Intranasal microemulsions, gels and microspheres have gained increased interest in recent years as a delivery system for protein and peptides through the nasal route. Thus this review focuses on nasal drug delivery, various aspects of nasal anatomy and physiology, nasal drug absorption mechanisms, various nasal drug delivery systems, and their applications in drug delivery.

An overview on: trade-related aspects of intellectual property rights.

The World Trade Organisation’s (WTO) Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) substantially changed the international intellectual property regime by introducing the principle of minimum intellectual property standards. In effect, this principle means that any intellectual property agreement negotiated subsequent to TRIPS among and/or involving WTO members can only create higher standards – commonly known as “TRIPS plus”. The TRIPS-plus concept covers both those activities aimed at increasing the level of protection for right holders beyond that which is given in the TRIPS Agreement and those measures aimed at reducing the scope or effectiveness of limitations on rights and exceptions. Such intellectual property rules and practices have the effect of reducing the ability of developing countries to protect the public interest and may be adopted at the multilateral, plurilateral, regional and/or national level. The TRIPS Agreement addresses a wide range of intellectual property subject matter areas (copyright, trademark, patent, and so forth). It also covers competitive markets, enforcement measures, dispute settlement, and transitional arrangements. This Module provides an introduction to these various aspects of the TRIPS Agreement, and seeks to focus on the kinds of questions that should be asked when approaching dispute settlement. In some areas, the questions are answered, but the entire field of intellectual property rights protection, including enforcement measures, cannot be covered in a single Module or short course. Moreover, the questions will change along with the technologies that form the subject matter of intellectual property rights protection. The objective of this Module is to provide sufficient background so that as specific issues arise, the diplomat or lawyer understands how to approach them.

Pregnancies in adolescents: fetal, neonatal and maternal outcome.

We studied the perinatal morbidity and mortality among adolescent pregnancies in the semi-urban population of Gorakhpur. The number of eligible couples (females 15-44 yrs) were 24,000. Out of 430 adolescent married girls, 242 (56.3%) became pregnant during the study period. Nineteen (7.8%) of adolescent pregnancies were in the maternal age group less than 15 years and 110 (45.5%) and 113 (46.7%) pregnancies were in the age group 15-17 yrs and 17-19 yrs, respectively. The incidence of low birth weight babies was 67.3% of all live births. Infections during neonatal period, congenital anomalies and birth injuries were seen in 21.6, 8.6 and 13.1% newborns, respectively. Neonatal mortality rate was 136.2/1000 live births. Three adolescent mothers died during pregnancy or puerperium due to causes related to pregnancy. The incidence of LBW, neonatal and maternal morbidity and mortality associated with adolescent pregnancies were significantly higher.