*Article* **Development and In Vitro-In Vivo Evaluation of a Novel Sustained-Release Loxoprofen Pellet with Double Coating Layer**

#### **Dongwei Wan 1, Min Zhao 1, Jingjing Zhang 1 and Libiao Luan 2,\***

Received: 7 May 2019; Accepted: 3 June 2019; Published: 5 June 2019

**Abstract:** This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the surface of a LXP conventional pellet, and to compare its performance in vivo with an immediate release tablet (Loxinon®). A three-level, three-factor Box-Behnken design and the response surface model (RSM) were used to investigate and optimize the effects of the citric acid content in the sub-layer, the sub-layer coating level, and the outer ADEC coating level on the in vitro release profiles of LXP sustained release pellets. The pharmacokinetic studies of the optimal sustained release pellets were performed in fasted beagle dogs using an immediate release tablet as a reference. The results illustrated that both the citric acid (CA) and ADEC as the dissolution- and diffusion-rate controlling materials significantly decreased the drug release rate. The optimal formulation showed a pH-independent drug release in media at pH above 4.5 and a slightly slow release in acid medium. The pharmacokinetic studies revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets was achieved, with a relative bioavaibility of 87.16% compared with the conventional tablets. This article provided a novel concept of two-step control of the release rate of LXP, which showed a sustained release both in vitro and in vivo.

**Keywords:** sustained release pellets; double coating layer; loxoprofen; citric acid; pharmacokinetic studies


*4.2. Hypothesis Test*

The *hypothesis test* (S1) of the statistical partitioning heuristic follows the same methodology as in both calibration procedures, and it can incorporate the data correction for rounding errors or not (S4). The test still assesses whether or not *ln*(*RDij*/*PDij*) is normally distributed by employing Blom scores and the table of Looney and Gulledge. If the correction for *rounding* errors (S4) is also taken into account, it still corresponds to the averaging of the Blom scores for all clusters of tied points. Therefore, it is not necessary to elaborate on each aspect of the S0 and S4 procedures in detail.

Recall that the hypothesis (S1) was also tested in steps S2 and S3 of the calibration procedures, after the removal of all on-time points and a portion of tardy points to incorporate the effect of Parkinson. As a matter of fact, the major difference between the calibration procedures and the new statistical partitioning method lies exactly in the treatment of the data for the Parkinson's effect (S2 or S3). The (extended) calibration method aims at removing data from the project clusters to be never used again (since it follows the Parkinson effect) and only continues the hypothesis testing on the remaining portion of the data. However, the new statistical partitioning heuristic does not automatically remove data points from the clusters, but, instead, aims at splitting each partition into two separate clusters (subpartitions) and then continues testing the same hypothesis on both partitions. This iterative process of splitting and testing continues until a certain stop criterion is met, and the data of all created subpartitions that pass the test are kept in the database. More precisely, at a certain moment during the search, each subpartition will be either accepted (i.e., the data follow a lognormal distribution) or rejected (i.e., the data do not follow a lognormal distribution or the sample size of the cluster has become too small). As shown in Figure 4, we have set the minimum sample size to 3 since partitions containing too few points may get too easily accepted. The way partitions are split into two subpartitions is defined by two newly developed statistical strategies (selection and stopping), which will be discussed in the next section.


**7.3 Cost-benefit analysis of remote surgery for patients**

The hospitalization costs of remote surgery patients include two types of costs: direct costs and indirect costs. Direct costs include medical and non-medical expenses. Medical expenses include various treatment-related expenses, the cost depreciation of the surgical robot system, and personnel costs of remote surgical physicians. Non-medical expenses include living, transportation, and accommodation expenses during hospitalization. Indirect costs include family members' lost income, patients' lost income, and other costs. For remote surgery patients, the structure of

these costs is the same, but the amount of cost consumption will differ. Conducting remote surgery treatment will reduce the patient's indirect cost expenditure.


**Abstract**

This review aims to identify pitfalls and insights into the nature of sustainable leadership frameworks and propose a new framework for organisational longevity and the sustenance of society and the environment. A background literature review was conducted to purposively select seminal and influential frameworks of sustainable leadership. Pitfalls and insights in these frameworks were delineated and developed into broader categories using open coding and constant comparison. The findings reveal that the pitfalls of sustainable leadership at the individual level include a lack of accurate sustainability self-awareness, failure to realise the diversity of strategic thinking competencies and a shaky foundation of sustainability literacy. In contrast, ethical competence and system literacy constitute vital insights. At the organisational level, it is revealed that lack of sustainability human resources, absence of a sustainable organisational culture model and lack of clarity on the value of social capital are pitfalls of sustainable leadership. Organisational-level insights in sustainable leadership hinge on stakeholder centricity, the complexity of driving sustainability innovation and managing the complexity of internal and external interdependencies. A new integrative model of sustainable leadership is proposed with various dimensions for leaders to significantly propagate and model sustainable leadership in the organisation.

**Keywords:** sustainable leadership, systems leadership, sustainability


1.1.3 Fabric

A two-dimensional object having thin thickness, large length, and wide width formed by interweaving and interlacing textile fibers and yarns by a certain method is the flat fabric. There are a variety of fabrics (as shown in Figure 5); they could have various materials, forms, colors, structures, and formation methods.

According to the forming methods, the fabrics can be divided into woven fabric, knitted fabric, and nonwoven fabric. The woven fabric is composed by warp and weft yarns arranged perpendicularly to each other according to some organization rules. The knitted fabric is formed by the yarns bent into a loop. Nonwoven fabrics are reinforced by oriented or randomly arranged fiber webs.


*2.2. Passive Avoidance Test*

The passive avoidance test was conducted to determine the ability of working memory and learning. As shown in Figure 2, there was no significant difference among the three groups.


**2. Obufia community since oil extraction**

Obufia is one of the 16 communities, which comprise Egbema. While three of the communities are in Rivers State, the rest are in Imo State. A few features may be identified as common to these communities in Egbema. There are visible lines of pipelines crisscrossing the terrains, a good number of which are dilapidated and abandoned. Apart from that, oil wells can still be found across the communities. Some of them are still productive, while others are dried up. There are some communities that host flow stations of the oil firms operating in the area. Some of these flow stations have gas flaring sites as well, and are often fenced with barbed wires and perimeter fences to restrict movement around them.

On its own, Obufia has some peculiar features. Despite that official population figures hardly exist, by 2006 the population census of Ohaji/Egbema LGA, to which Obufia belongs, places it at about 183,000 (One hundred and eighty-three thousand). Roughly however, the population of Obufia may be placed at about 18–10,000. Obufia, or any other autonomous community in Egbema-Imo may not be correctly depicted as ethnically mixed. About 98 percent of the population is Igbo speaking. Less than 8 percent of this majority, may be regarded as outsiders in Obufia, having not been either born, or adopted into the community. In other words, only about 8 percent of the local population of Egbema-Imo belong to the category of the people, whom those born or adopted into any Egbema community regard as *U*̣*mu*̣*isu*. *U*̣*mu*̣*isu* (Literally, descendants of *Isu*) refers to another Igbo group found around the Orlu axis of Imo State. The Egbema tradition has it that the *Isu* people came into Egbema for business reasons. Such businesses included collecting wild vegetable, *o*̣*kazi*̣/*o*̣*kashi*̣, and palm fruits. Others included fishing, or engaging in jobs, which the local people were not very adept at. The manual cultivation of farmland is one example of such jobs. Overtime, the term came to be applied to every other ethnic Igbo, who is neither born to or adopted in any Egbema community.

The rest of the population in Obufia are non-Igbo speaking people who are hired by the oil companies. They also include people who have been employed by privately

#### *Responding Creatively to Faulty Corporate Social Responsibility Practices: The Case of Nigeria's… DOI: http://dx.doi.org/10.5772/intechopen.106249*

owned establishments in Obufia, such as schools or grain mills. People who engage in assorted forms of small-scale business, such as dry meat (*suya*) vending, or hawking of articles of assorted kinds belong to this category as well. Most times these hawkers either head-load these articles, or carry them in push-trucks. Within Obufia, or any other community in Egbema-Imo, one does not expect to hear people carrying out conversations in English, as may be the case in several places across Nigeria, where the population is ethnically mixed.

SPDC yard, locally known as Location is situated in Obiakpu, a neighboring community to Obufia, both in Egbema. The Location is less than two miles from the border of Obufia and Obiakpu. SPDC has several oil wells, flowstations and pipelines—both underground and over ground—within Obufia. This is the major factor connecting SPDC and the rest of the communities in Egbema.

The community has all but a few of its narrow streets richly coated with quality nylon tar. The access road into the community from the nearest city, which is also the highway connecting the community to other Egbema communities in Rivers State, is hardly in any condition comparable in quality to the narrowly paved streets within the community. For the most part, the narrow highway was dotted by potholes, making motoring cumbersome. The community also has a very nicely built state managed secondary school, and a not-so-good looking state owned primary school. There are a few other privately owned schools there as well. Many potable water points are quite conspicuous across the community. Some of these water points were constructed and handed over to the community, courtesy of SPDC. Some were connected to boreholes drilled in private homes. Thus, access to water by members of the community is not so difficult. Quite recently, the town has added a magnificent civic centre, alongside a community health clinic to its credit. Most of these modern facilities came courtesy of the oil business taking place in the community. They would have been funded by either the SPDC or the special state commissions such as the Niger Delta Development Commission (NDDC) and the Imo State Oil Producing Areas Development Commission (ISOPADEC). Obufia community has also benefited from the oil companies and the special commissions in other ways. SPDC has constructed a town hall and awards scholarships to successful Obufia secondary school leavers each year, just as it liaises with different associations of the community for development.

I came into this field intending to observe and interview the actors I believed were implicated in one way or the other by the oil extraction business and sundry activities connected to it. Deploying purposive sampling method, I examined actors such as the SPDC public relations officer, the traditional ruler, and state representatives in the community, including the Local Government Chairman, and the community representative at the State House of Assembly. It means that these were significant to the objectives of my study. Apart from the latter, other figures that I considered directly implicated in the oil extraction issues, included state political office holders, and officers in the special state commissions—ISOPADEC and NDDC—established for the Niger Delta.