Biomedical subjects

Paras Jain

Publications and source records attributed to Paras Jain.

4 recordsLinked to original sources

PubMed2006

Novel sustained release, swellable and bioadhesive gastroretentive drug delivery system for ofloxacin.

Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from upper gastrointestinal tract and improve the bioavailability of medications that are characterized by a narrow absorption window. A new gastroretentive sustained release delivery system was developed with floating, swellable and bioadhesive properties. All these properties were optimized and evaluated. Various release retarding polymers like psyllium husk, HPMC K100M and a swelling agent, crosspovidone in combinations were tried and optimized to get the release profile for 24 h. Formulations were evaluated for in vitro drug release profile, swelling characteristics and in vitro bioadhesion property. The in vitro drug release followed Higuchi kinetics and the drug release mechanism was found to be of anomalous or non-Fickian type. For the developed formulation, the value of n was found to be 0.5766 while for the marketed formulation the value was 0.5718 indicating the anomalous transport. The high water uptake leading to higher swelling of the tablet supported the anomalous release mechanism of ofloxacin. The similarity factor f2 was found to be 91.12 for the developed formulation indicating the release was similar to that of the marketed formulation (Zanocin OD). The swelling properties were increased with increasing crosspovidone concentration and contributed significantly in drug release from the tablet matrix. The bioadhesive property of the developed formulation was found to be significant (P < 0.005) in combination as compared to HPMC K100M and psyllium husk alone.

Administration, Oral↗

PubMed2006

Indispensable, functionally complementing N and C-terminal domains constitute site-specific topoisomerase I.

Mycobacterium smegmatis topoisomerase I differs from the typical type IA topoisomerase in many properties. The enzyme recognizes both single and double-stranded DNA with high affinity and makes sequence-specific contacts during DNA relaxation reaction. The enzyme has a conserved N-terminal domain and a highly varied C-terminal domain, which lacks the characteristic zinc binding motifs found in most of the type I eubacterial enzymes. The roles of the individual domains of the enzyme in the topoisomerase I catalyzed reactions were examined by comparing the properties of full-length topoisomerase I with those of truncated polypeptides lacking the conserved N-terminal or the divergent C-terminal region. The N-terminal larger fragment retained the site-specific binding, DNA cleavage and religation properties, hallmark characteristics of the full-length M.smegmatis topoisomerase I. In contrast, the non-conserved C-terminal fragment lacking the typical DNA binding motif, exhibited non-specific DNA binding behaviour. The two polypeptide fragments, on their own do not catalyze DNA relaxation reaction. The relaxation activity is restored when both the fragments are mixed in vitro reconstituting the enzyme function. These results along with the DNA interaction pattern of the proteins implicate an essential role for the C-terminal region in single-strand DNA passage between the two transesterification reactions catalyzed by the N-terminal domain.

Bacterial Proteins↗

PubMed2005

Development of sustained release gastroretentive drug delivery system for ofloxacin: in vitro and in vivo evaluation.

Sustained release (SR)-gastroretentive dosage forms (GRDF) enable prolonged and continuous input of the drug to the upper parts of the gastrointestinal (GI) tract and improve the bioavailability of medications that are characterized by a narrow absorption window. A new strategy is proposed for the development of gastroretentive dosage forms for ofloxacin preferably once daily. The design of the delivery system was based on the sustained release formulation, with floating and swelling features in order to prolong the gastric retention time of the drug delivery systems. Different polymers, such as psyllium husk, HPMC K100M, crospovidone and its combinations were tried in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for buoyancy lag time, duration of buoyancy, dimensional stability, drug content and in vitro drug release profile. It was found that dimensional stability of the formulation increases with the increasing psyllium husk concentration. It was also found that in vitro drug release rate increased with increasing amount of crospovidone due to the increased water uptake, and hence increased driving force for drug release. The optimized formulation was subjected to stability studies at different temperature and humidity conditions as per ICH guidelines. In vivo studies were carried out for the optimized formulation in 24 healthy human volunteers and the pharmacokinetic parameters of developed formulations were compared with the marketed once daily (Zanocin) formulation. Based on the in vivo performance in a parallel study design in healthy subjects, the developed formulation shows promise to be bioequivalent to the marketed product (Zanocin). The percent relative bioavailability of developed formulation was found to be 97.55%.

Absorption↗

PubMed2005

An atypical type II topoisomerase from Mycobacterium smegmatis with positive supercoiling activity.

Topoisomerases are essential ubiquitous enzymes, falling into two distinct classes. A number of eubacteria including Escherichia coli, typically contain four topoisomerases, two type I topoisomerases and two type II topoisomerases viz. DNA gyrase and topoisomerase IV. In contrast several other bacterial genomes including mycobacteria, encode for one type I topoisomerase and a DNA gyrase. Here we describe a new type II topoisomerase from Mycobacterium smegmatis which is different from DNA gyrase or topoisomerase IV in its characteristics and origin. The topoisomerase is distinct with respect to domain organization, properties and drug sensitivity. The enzyme catalyses relaxation of negatively supercoiled DNA in an ATP-dependent manner and also introduces positive supercoils to both relaxed and negatively supercoiled substrates. The genes for this additional topoisomerase are not found in other sequenced mycobacterial genomes and may represent a distant lineage.

Ciprofloxacin↗