Research Article
Volume 1 Issue 1 - 2014
The Impact of the Polymer Content on the Kinetics of Propranolol HCl from Buccal Adhesive Tablets
Majid Saeedi1* and Katayoun Morteza-Semnani2
1Department of Pharmaceutics, Mazandaran University of Medical Science, Iran
2Department of Medicinal Chemistry, Mazandaran University of Medical Science, Iran
*Corresponding Author: Majid Saeedi, Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, 18th. Km. of Khazar road, PO Box: 48175-861, Sari, Iran.
Received: November 5, 2014; Published: December 1, 2014
Citation: Majid Saeedi and Katayoun Morteza-Semnani. “The Impact of the Polymer Content on the Kinetics of Propranolol HCl from Buccal Adhesive Tablets”. EC Pharmaceutical Science 1.1 (2014): 4-15.
Abstract
The relation between Higuchi rate constant (k) and amount of polymer (mg) in hydrophilic matrix tablets of propranolol HCl was evaluated. Each tablet composed of 80mg propranolol, 80mg Hydroxypropyl methyl cellulose (HPMC) K4M, Polycarbophil AA1, Carbopol 934P, and Lactose or Dicalcium phosphate with different ratios. After preparing several formulations the release profiles were evaluated. The dissolution data were fitted to Higuchi model. A new relationship between k and polymer content was found in hydrophilic matrices. The results showed the relationship between HPMC K4M (mg) and k in the presence of constant amount of polycarbophyl, this relationship showed no differences in reciprocal, logarithmic and content of polymer (P > 0.05). This relationship was observed between polycarbophyl content and k in the presence of constant amount of HPMC K4M (P < 0.001). In formulations with constant amount of lactose, these results showed that there is relation between logarithm of polycarbophyl amount in formulations and log k (P < 0.05), and this relationship was also obtained for HPMC K4M containing formulations in the presence of dicalcium phosphate (P < 0.05). In formulations which containing constant amount of Carbopol 934P, HPMC K4M content (mg) showed relationship with k (P < 0.01). In the presence of constant amounts of lactose, the logarithmic relationship was obtained with Carbopol 934P content (P < 0.05). In this study, the direct relationship between k and polymer content in some hydrophilic matrices was obtained.
Keywords: Kinetic; Higuchi; HPMC K4M; Carbopol; Polycarbophyl
Introduction
The hydrophilic matrices are one of the most used controlled delivery systems in the world, due to the simple technology and low cost. Its study is a difficult task due to its complex and disordered structure. These hydrophilic matrices are widely accepted because of their biopharmaceutical and pharmacokinetics advantages over conventional dosage forms [1]. A number of publications have reported studies about the mechanisms of drug release from hydrophilic matrices. Nevertheless, nowadays, the mechanisms of drug release from these systems continue to be a matter of debate [2]. Significant experimental and theoretical work has been performed to accurately model drug transport and reveal the mechanisms of drug release from these systems. Despite the complexity of the phenomena involved, two well known approaches are used extensively and successfully for the analysis of drug release data in these systems. The first approach relies on the famous Higuchi equation, which the fraction of drug released is proportional to the square root of time. The second approach relies on the semi-empirical, used extensively and successfully for the analysis of the first 60% of the release curves as Korsmeyer-peppas model [3,4].
Various attempts have been made to achieve the prolonged release of active agents; prominent amongst these is the enhanced retention of formulations at their intended site of action by means of bioadhesive formulations [5]. Recent years have seen an increasing interest in the development of novel mucoadhesive buccal dosage forms [6,7]. The buccal mucosa has been investigated for local and systemic delivery of therapeutic peptides and other drugs that are subjected to first pass metabolism or are unstable within the rest of the gastrointestinal tract [8-10]. Bioadhesive formulations use polymers as the adhesive component. These formulations are often water soluble and when in a dry form attract water from the biological surface and this water transfer leads to a strong interaction. These polymers also form viscous liquids when hydrated with water that increases their retention time over mucosal surfaces and may lead to adhesive interactions. Bioadhesive polymers should possess certain physicochemical features including hydrophilicity, numerous hydrogen bond-forming groups, flexibility for interpenetration with mucus and epithelial tissue, and viscoelastic properties [11]. Mucoadhesive materials are hydrophilic macromolecules containing numerous hydrogen bond-forming groups [12]. Bioadhesive polymers such as sodium carboxymethyl cellulose, carbopol 934, polycarbophil (PAA), hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), carrageenan and poloxamer are suitable for use in buccal adhesive preparations. These polymers when hydrated with water can adhere to the oral mucosa and withstand salivation, tongue movements and swallowing for a significant period of time [13]. These polymers not only cause the adhesion effects, but also control the release rate of drug [14]. Polycarbophil and HPMC are suitable polymers for formulation the bioadhesive tablets. These polymers in addition of bioadhesion effects, decrease release rate and change kinetic of drug release from mucoadhesive tablets [15-17]. Propranolol is subjected to first pass effect; therefore, formulation of buccal-adhesive dosage form can circumvent this effect [6].
The kinetics of drug release from matrices were examined for both freely soluble and poorly water soluble drugs, and mathematical models have been developed for expression the mechanism of drug release. One of these models is Higuchi square root of time model [18]. Previous studies showed relationship between dissolution rate constant in Higuchi model (k) and polymer content. These studies showed a logarithmic relationship between k and polymer content or reciprocal relation between k and amount of polymer (mg) [19]. The objectives of this study were to examine the in vitro release characteristics of propranolol hydrochloride from different buccal adhesive tablets and evaluation the relationship between Higuchian release rate and polymer quantity in the presence of lactose and dicalcium phosphate as water soluble and insoluble fillers. In this research, a new relation between k and amount of polymer was evaluated for the first time.
Materials and Methods
Materials
Propranolol HCl was USP grade (Rouz Daru Co., Iran). Hydroxy propyl methyl cellulose K4M viscosity grade (Colorcon Co., UK), polycarbophil (Noveon AA1), and carbopol 934P (B.F. Goodrich, USA) were used as mucoadhesive polymers. Dicalcium phosphate and lactose (Merck, Germany) were used as required as fillers. Magnesium stearate (Merck, Germany) was used as lubricant.
Tableting
Formulation composition of different buccal adhesive tablets of propranolol hydrochloride has been shown in Table 1. Compaction was accomplished using direct compression (Korch single punch model 9219-77, Germany) of the blends that has been thoroughly mixed for 15min using a cubic mixer (Erweka, Germany). The punch No.9 in diameter was used for Tableting. Formulations 1-11 composed of 80mg of different ratios of HPMC K4M, Polycarbophyl (PAA1) and lactose and in formulations 12-16, Dicalcium phosphate (DCP) was used as filler. This composition in formulations 17-23 was 80mg of drug and 80mg of different ratios of HPMC K4M, Carbopol 934P (Car. 934P) and lactose. All of formulations had magnesium stearate (1%) as lubricant.


Formulation Code Formulation Composition (mg)
Drug HPMC K4M PAA1 Car. 934P Lactose DCP Mg Stearate
F1 80 72 4 - 4 - 1.6
F2 80 68 4 - 8 - 1.6
F3 80 64 4 - 12 - 1.6
F4 80 56 4 - 20 - 1.6
F5 80 60 16 - 4 - 1.6
F6 80 60 12 - 8 - 1.6
F7 80 60 8 - 12 - 1.6
F8 80 60 4 - 16 - 1.6
F9 80 68 8 - 4 - 1.6
F10 80 64 12 - 4 - 1.6
F11 80 56 20 - 4 - 1.6
F12 80 72 4 - - 4 1.6
F13 80 68 4 - - 8 1.6
F14 80 64 4 - - 12 1.6
F15 80 60 4 - - 16 1.6
F16 80 56 4 - - 20 1.6
F17 80 72 - 4 4 - 1.6
F18 80 68 - 4 8 - 1.6
F19 80 64 - 8 8 - 1.6
F20 80 56 - 8 16 - 1.6
F21 80 56 - 20 4 - 1.6
F22 80 56 - 16 8 - 1.6
F23 80 56 - 12 12 - 1.6
Table 1: Formulation composition of different buccal adhesive tablets of propranolol HCl. HPMC K4M = Hydroxy Propyl Methyl Cellulose K4M, PAA1 = Polycarbophil, Noveon AA1, Car. 934P = Carbopol 934P, DCP = Dicalcium Phosphate.
Evaluation of tablets
Tablet properties (crushing strength, mass variation, and friability) were determined by standard procedure [20]. The tensile strength (T) of tablet which is a measure of the stress necessary to cause diametric fracture of the compact was determined from the mean data obtained from the hardness test carried out on the tablets (n = 10) using the Erweka hardness tester (TBH 30 MD, Germany). The T values were computed from equation below [21]:
Where, P is the load applied on the tablet that causes diametric fracture of the tablet of diameter, D, and t is the tablet thickness (m).
Dissolution rate study
The dissolution rates were evaluated by apparatus type II of USP dissolution tester (Caleva 8ST, Germany). For study of drug release from only one side of tablets, the glass dies were used. For this purpose every die filled with melted wax, and before solidification, the tablets put in semisolid wax, as only one side of them were in contact with dissolution medium. In this evaluation six tablets of each formulation which were placed in the die, and were at the bottom of the vessel with 900 ml of phosphate buffer with pH 6.8 evaluated at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7 and 8h after the beginning of dissolution test. Sample (10 ml) was taken and immediately replaced with an equivalent volume of dissolution medium. Samples were filtered and assayed at 288.8 nm by using UV spectrophotometer (Shimadzo 60A, Japan).
In vitro release data analysis
The most widely model to describe drug release from matrices, derived from Higuchi for a planar matrix; however it is applicable for systems of different shapes also:
(1)
Where is the fractional release of the drug, t is the release time, and k is a constant
incorporating structural and geometric characteristic of the controlled release device [22,23].
Previous studies showed relationship between release rate and polymer quantity. Examination of some drugs showed that when the polymer fraction increases, the dissolution of the drug decreases. The generalized relationship for each of these lines can be expressed by the following relationship [24]:
(2)
Where k is Higuchian release rate (min-1/2), M is slope of the derived line, W is weight of HPMC (mg), and c is constant.
Other studies on different drugs showed a linear relationship existed between the logarithm of the tablet polymer content and the logarithm of the release rate in Higuchi model [25]:
(3)
Where k and W is like equation 2, M' is the slope of line and c' is constant [19].
In this study a new equation was presented for relation between k and polymer content.
(4)
Where k and W is like equations 1 and 2, M˝ is the slope of line and c˝ is a constant.
Statistical analysis
Statistical analysis was carried out by using analysis of variance (ANOVA) with computer software SPSS 10. Tukey-Kramer multiple-comparison tests were used to compare group's data. P values ≤ 0.05 were considered significant.
Results
Tablet characteristics
Table 2 shows the characteristics of investigated tablets. These results show that all of formulations have the suitable friability and hardness. The content uniformity was in the Pharmacopeial criteria.


Formulation Code Characteristics of Evaluated Tablets
Hardness* (kg.cm-2) (n=10) Friability*
(%w/w) (n=10)
Tensile Strength*
(MN.m-2) (n=10)
Assay* (%) (n=20)
F1 8.9 ± 1.2 0.51 ± 0.05 5.24 ± 0.70 98.62 ± 1.51
F2 9.8 ± 0.7 0.31 ± 0.04 5.92 ± 0.11 96.37 ± 3.00
F3 11.7 ± 0.8 0.15 ± 0.06 7.19 ± 0.55 97.62 ± 3.62
F4 9.7 ± 0.7 0.25 ± 0.04 6.13 ± 0.44 98.62 ± 3.62
F5 9.6 ± 1.1 0.35 ± 0.07 5.66 ± 0.65 98.00 ± 4.00
F6 10.1 ± 0.8 0.28 ± 0.05 6.05 ± 0.48 100. 15 ± 3.12
F7 6.4 ± 0.5 0.71 ± 0.06 3.90 ± 0.30 97.37 ± 2.87
F8 10.2 ± 0.9 0.18 ± 0.02 6.32 ± 1.79 99.75 ± 3.87
F9 11.3 ± 0.8 0.32 ± 0.03 6.72 ± 0.68 100.50 ± 3.87
F10 14.1 ± 0.7 0.17 ± 0.02 8.17 ± 0.41 97.62 ± 4.50
F11 6.4 ± 0.7 0.68 ± 0.07 3.65 ± 0.39 100.12 ± 4.73
F12 5.6 ± 0.3 0.81 ± 0.08 3.33 ± 0.17 99.50 ± 2.62
F13 6.7 ± 0.4 0.72 ± 0.06 3.98 ± 0.24 100.12 ± 3.87
F14 10.7 ± 0.7 0.27 ± 0.03 6.47 ± 0.42 99.25 ± 4.12
F15 10.9 ± 0.6 0.20 ± 0.02 6.70 ± 0.37 99.62 ± 4.15
F16 9.6 ± 0.4 0.25 ± 0.03 6.01 ± 0.25 100.75 ± 1.87
F17 9.1 ± 0.5 0.29 ± 0.03 5.59 ± 0.31 98.37 ± 2.37
F18 8.6 ± 0.7 0.75 ± 0.06 5.15 ± 0.42 99.50 ± 4.37
F19 8.6 ± 0.5 0.68 ± 0.07 5.11 ± 0.29 100.12 ± 3.37
F20 9.6 ± 0.4 0.48 ± 0.05 5.80 ± 0.24 99.25 ± 2.75
F21 6.7 ± 0.5 0.81 ± 0.07 4.16 ± 0.31 98.25 ± 2.12
F22 8.7 ± 0.4 0.47 ± 0.05 5.49 ± 0.25 100.25 ± 3.87
F23 9.0 ± 0.8 0.35 ± 0.03 5.63 ± 0.50 101.12 ± 2.25
Table 2: Characteristics of propranolol HCl prepared tablets.
*Data are shown as mean ± SD
Formulations with different amount of HPMC K4M and constant quantity of PAA1 in the presence of lactose
The results of kinetic evaluation of drug release from formulations F1-F4 (Figure 1) in Higuchi model have been presented in Table 3. The results showed relationship between reciprocal amounts, logarithm of polymer, and content of HPMC K4M (mg) and Higuchian release rate. The statistical analysis showed no significant differences between these equations (P>0.05):
(5)
(6)
(7)
Figure 1: Release profile of propranolol HCl from Formulations (F1-F4) with different amount of HPMC K4M and constant quantity of PAA1 in the presence of lactose (n = 4).
Formulation with different amount of PAA1 and lactose in the presence of constant quantity of HPMC K4M
The results of kinetic evaluation of drug release from formulations F5-F8 (Figure 2) in Higuchi model have been presented in Table 3. The results showed a relation between Higuchi release rate and polycarbophil quantity in equation 10 (P<0.001).
(8)
(9)
(10)
Figure 2: Release profile of propranolol HCl from Formulations (F5-F8) with different amount of PAA1 and lactose in the presence of constant quantity of HPMC K4M (n = 4).
Formulation with different amount of HPMC K4M and PAA1 in the presence of constant quantity of lactose
The results of kinetic evaluation of drug release from formulations F9, F10, F5, and F11 (Figure 3) in Higuchi model have been presented in Table 3. The results showed a relationship between logarithms of PAA1 with logarithm of Higuchian release rate in equation 13 (P<0.05):
(11)
(12)
(13)
k = Rate constant in Higuchi equilibrium, r2 = Determination constant of fitting of data in Higuchi equilibrium, ss = Sum of squares of deviations, n = Number of samples
Figure 3: Release profile of propranolol HCl from Formulations (F5, F9-F11) with different amount of HPMC K4M and PAA1 in the presence of constant quantity of lactose (n = 4).
Formulation Code Polymer Content (mg) Kinetic Data in Higuchi Model
HPMC K4M PAA1 Car. 934P k (min-1/2) r2 ss
F1 72 4 - 1.67 0.992 6.47
F2 68 4 - 1.74 0.995 4.54
F3 64 4 - 1.77 0.993 6.25
F4 56 4 - 1.91 0.996 4.10
F5 60 16 - 1.04 0.996 1.24
F6 60 12 - 1.33 0.994 2.88
F7 60 8 - 1.61 0.994 4.55
F8 60 4 - 1.87 0.994 5.20
F9 68 8 - 1.50 0.995 3.18
F10 64 12 - 1.32 0.993 3.56
F11 56 20 - 0.98 0.999 0.39
F12 72 4 - 1.58 0.995 3.26
F13 68 4 - 1.60 0.996 2.97
F14 64 4 - 1.65 0.996 3.15
F15 60 4 - 1.74 0.996 3.73
F16 56 4 - 1.76 0.997 2.52
F17 72 - 4 1.64 0.994 4.56
F18 68 - 4 1.80 0.995 4.74
F19 64 - 8 1.89 0.994 6.60
F20 56 - 8 1.95 0.997 3.70
F21 56 - 20 1.04 0.997 0.86
F22 56 - 16 1.29 0.995 2.32
F23 56 - 12 1.49 0.996 2.81
Table 3: Kinetic constants, determination coefficients, and sum of squares of deviations following fitting of dissolution data to Higuchi model (n = 6).
Formulations with different amount of HPMC K4M and constant quantity of PAA1 in the presence of DCP
The results of kinetic evaluation of drug release from formulations F12-F16 (Figure 4) in Higuchi model have been presented in Table 3. The results showed a relationship between logarithms of amount of HPMC K4M (mg) and logarithm of Higuchian release rate (P<0.05):
(14)
(15)
(16)
Figure 4: Release profile of propranolol HCl from Formulations (F12-F16) with different amount of HPMC K4M and constant quantity of PAA1 in the presence of DCP (n = 4).
Formulations with different amount of HPMC K4M in the presence of carbopol 934P and Lactose
The results of kinetic evaluation of drug release from formulations F17-F20 (Figure 5) in Higuchi model have been presented in Table 3. The results showed a relationship between amounts of Car.934P with of Higuchian release rate (P < 0.01):
(17)
(18)
(19)
Figure 5: Release profile of propranolol HCl from Formulations (F17-F20) with different amount of HPMC K4M in the presence of carbopol 934P and Lactose (n = 4).
Formulations with different amount of carbopol 934P in the presence of HPMC K4M and Lactose
The results of kinetic evaluation of drug release from formulations F20-F23 (Figure 6) in Higuchi model have been presented in Table 3. The results showed a logarithmic relationship between amount of carbopol 934P (mg) and Higuchian release rate (P < 0.05):
(20)
(21)
(22)
Figure 6: Release profile of propranolol HCl from Formulations (F20-F23) with different amount of carbopol 934P in the presence of HPMC K4M and Lactose (n = 4).
Discussion
Controlled release by hydrophilic matrix remains a very versatile tool in the hands of the formulator and we can only look forward to greater formulation predictability as more and more fundamental studies become available. HPMC is a semisynthetic ether derivative of cellulose. It has been the dominant hydrophilic vehicle used in controlled release dosage forms because of its non-toxic nature, ease of compression, and accommodation to high levels of drug loading. It is desirable to predict the drug release from HPMC matrices with enough accuracy in the design of drug containing HPMC matrices [25]. Fu et al. proposed an empirical relationship between drug release rate and HPMC concentration [26].
The Higuchi model has been an invaluable framework over its 50-year history for developing large parts of modern drug delivery technology. It captures the essence of what governs drug release from a permeable matrix when the drug loading is well in excess of its solubility limit and allows prediction of release rates with good accuracy in most cases. It has endured because of its simplicity. Naturally, it embodies a number of assumptions and approximations, some of which are not so obvious [27]. Drug release rate (Higuchi-type release rate) was correlated with the reciprocal HPMC concentration in their empirical model. Shah et al. [28] reported a method for the prediction of the fraction drug release as a function of HPMC concentration and release time [28].
This research has elaborated a new relationship between release rate of drug and amount of mucoadhesive polymer in propranolol buccal adhesive tablets. Some studies had been shown a relationship between dissolution rate constant in Higuchi model (k) and reciprocal amount of polymer in hydrophilic matrices. Ford et al. [25] showed this relation is valid when applied to drugs of diverse aqueous solubility, provided that square time release kinetics are approximately followed [24]. The relation between log k and logarithm of polymer content had been obtained in hydrophilic matrices containing HPMC too. Ford et al. [25] studied hydrophilic matrices of Propranolol hydrochloride and aminophylline which prepared by several grades of HPMC. A straight line relationship was established between the logarithm of the tablet HPMC content and the logarithm of release rates (mg.min-1/2), enabling release rates to be predicted for a variety of different drug substances [25]. In this research these equations and relation between k and amount of polymer was examined for dissolution data in propranolol buccal adhesive tablets.
In formulations F1-F4 with constant quantity of PAA1 in the presence of lactose, no significant differences were observed between three equations (equations 5-7). Evaluation of the equations 6 and 7 showed a similar relation too. In formulations F5-F8 with different amount of PAA1, the best fit was observed in new relationship equation between k and amount of PAA1. This different was very manifest. In formulations with different amount of HPMC K4M and PAA1 in the presence of lactose (Table 3) the logarithmic relationship was observed. In these formulations the relation between k and amount of polymer (equation 13) was significant. In formulations F12-F16 with different amount of HPMC K4M in presence of carbopol 934P, the relation between k and amount of HPMC K4M was observed too (equation 19). In other formulations, this new relationship was fitted too.
Within the context of hydrophilic polymeric matrices containing water-soluble drug, excipients should not be regarded as neutral or simple additives as they are certainly capable of altering water penetration, erosion and hence mechanism of release. The role of gel layer and its rate of growth are central and fundamental to define various fronts and understand the operating release mechanism [29].
Conclusion
It can be concluded from this study that the kind and ratio of bioadhesive polymers have synergistic effect on controlling release rate and kinetic of propranolol HCl from evaluated buccal adhesive tablets. This study showed that the direct relation between k and amount of polymer should consider for prediction and regulating of release rate in hydrophilic matrices.
Acknowledgements
Some parts of this work were supported by a grant from the research and technology council of the Mazandaran University of Medical Sciences.
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Copyright: © 2014 Majid Saeedi., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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PMCID: PMC5450819


EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840


EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344


EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476


EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658


EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489


EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278


EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108


EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571


EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333


EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883


EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001


EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937


EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723


EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726


EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603


EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646


EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616


EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290


EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226


EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812


EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268


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