Printer Friendly

Production of Doxycycline-Loaded Gelatin Microspheres Through Thermal Treatment in Inverse Suspensions.

Doxycycline is a broad-spectrum antibiotic. The development of a polymer matrix that can allow for the controlled release of this drug can bring many benefits to veterinary and human medicine. For this reason, in the present study doxycycline was encapsulated in situ with gelatin through thermal treatments performed in inverse suspension, using distinct gelatin concentrations in the suspended aqueous phase. To characterize the performances of the obtained products, controlled release tests were performed. The effect of adding formaldehyde and glucose into the reaction medium to enhance gelatin crosslinking was analyzed, although obtained results indicated that addition of crosslinking agents is not necessary because addition of doxycycline is sufficient to promote the physical gelatin crosslinking.


Doxycycline (DOX) is a broad-spectrum tetracycline antibiotic and is effective both in human and veterinary medicine [1]. Some of the diseases treated with doxycycline are Lyme disease, periodontitis, gonorrhea (in penicillin-allergic patients) and canine and human ehrlichiosis [2]. Besides, doxycycline is a cheap antibiotic, when compared to other tetracyclines, which makes this drug attractive for different research purposes [3].

When used for treatment of canine ehrlichiosis, doxycycline is normally provided in capsules that must be administered orally twice a day for at least 21 days [4]. This can cause many problems during the long animal treatments, especially when animals present aggressive behavior. Although intravenous and intramuscular DOX formulations are also available, the medication is usually administered orally because doxycycline can cause tissue irritation when injected [5]. For this reason, development of a product that can allow for the controlled release of doxycycline can bring many benefits to veterinary and human medicine, allowing for reduction of the drug administration frequency.

The use of gelatin in drug encapsulation applications has been encouraged because of its good biocompatibility, biodegradability, low toxicity, and inexpensiveness [6]. Besides, as gelatin is a protein, its multiple functional groups can be crosslinked (at least in principle), allowing for production of hydrogels that can be used for formulation of drug controlled release systems. Most crosslinking agents already reported to modify the gelatin properties, however, are toxic, including glutaraldehyde [7-9], formaldehyde [10, 11], glyoxal [11, 12], and carbodiimides [13, 14]. As a consequence, these chemical compounds should be avoided when pharmaceutical applications are pursued. To replace these toxic compounds for other nontoxic gelatin crosslinking agents, many studies have proposed the use of natural sugars for gelatin crosslinking, including dextran [15-17], fructose [18], and glucose [18-20].

Since gelatin and doxycycline are both soluble in water and gelatin presents many competitive advantages when compared to alternative synthetic and natural materials [6], gelatin and doxycycline seem to constitute a proper combination for development of drug controlled release applications. In spite of that, it is important to emphasize that gelatin has never been used for encapsulation of doxycycline in previous investigations. It must be noted that encapsulation of doxycycline in gelatin matrices would not only allow for reduction of the number of medication doses, but also would allow for potential reduction of tissue irritation, as the drug would not be in direct contact with the living tissues.

Based on the previous remarks, in the present study doxycycline is encapsulated in situ with gelatin through thermal treatments performed in inverse suspension, using formaldehyde and glucose as crosslinking agents. Formaldehyde is used here for benchmarking purposes only, as it has been used as a gelatin crosslinking agent in previous investigations [10, 11]. Particularly, the effects caused by the interaction between gelatin and doxycycline and addition of formaldehyde and glucose into the reaction system are investigated. Finally, to characterize the performances of the obtained products, controlled release tests are also performed.



Pigskin gelatin (240-270 Bloom), PhEur gelatin, SPAN[R] 80 and D-(+)-Glucose ACS reagent were purchased from Sigma-Aldrich (Rio de Janeiro, Brazil) as pharmaceutical grades. Acetone (99.5%), propylene glycol (99.5%), formaldehyde (in aqueous solutions with concentrations of 36.5-38 wt%), ethanol (95%) and sodium dodecyl sulfate (SDS, 99%) were obtained from VETEC (Rio de Janeiro, Brazil). Sunflower oil was purchased from Liza (Rio de Janeiro, Brazil) as a nutritional grade. Doxycycline hyclate (99%) was purchased from Pharma Nostra (Goias, Brazil). All reagents were used as received, without further purification.

Microparticles Production

Initially, the specified amounts of glucose and doxycycline were dissolved in 10 g of distilled water in a glass flask at 60[degrees]C. Then, gelatin was added into the flask and the mixture was kept under magnetic stirring at 60[degrees]C until complete solubilization of the gelatin. The solution was then poured into a previously prepared mixture containing 40 g of sunflower oil and SPAN[R] 80 kept at the desired reaction temperature of 50[degrees]C ([T.sub.1]). The resulting inverse dispersion (reaction mixture) was kept under vigorous (~700 rpm) magnetic stirring for 20 min. After finishing the reaction run, the final product was cooled to 10[degrees]C and 50 mL of acetone were added into the flask for dehydration of the gelatin particles. The product was then filtrated, washed with abundant acetone (for removal of residual oil and water) and stored in desiccators at room temperature to prevent water absorption.

When formaldehyde was used as the crosslinking agent, 2 mL of a 10 wt% aqueous formaldehyde solution was added into the reaction flask after cooling to 10[degrees]C. Then, the reaction mixture was kept under magnetic stirring for an additional period of 2 h. After that, dehydration was performed as described before. When formaldehyde was used, the reaction temperature (T,) was set to 80[degrees]C, as recommended elsewhere [20].

Controlled Release Tests

In vitro controlled release tests usually must follow very strict protocols, although formal protocols are not available for parenteral applications [21-23]. For this reason, a protocol was developed and implemented to resemble the vertical diffusion cell test described by USP [24, 25], which seems appropriate to describe intramuscular applications. The test consists in putting a plastic cylindrical tube (internal diameter of 14.1 mm) in contact with the surface of 80 mL of phosphate saline buffer (PBS, with pH values ranging from 7.2 to 7.4), using glass vessels of standardized dimensions (Length of 73 mm and internal diameter of 41.4 mm). The tube was equipped with a dialysis membrane (CelluSep Regenerated Cellulose Tubular Membrane, United States), hydrated for at least 30 minutes in distilled water at 100[degrees]C. The test was performed after mixing 200 mg of the analyzed microparticles with 400 mg of propylene glycol and placing 150 mg of the prepared mixture into the cylindrical tube. The system was kept under continuous magnetic stirring (~150 rpm) at 37[degrees]C for 48 h. Aliquots of 2 mL were taken at regular sampling periods and stored in glass flasks at ambient temperature until test completion. Similar volumes of fresh PBS buffer were added into the vessel after sample withdrawal to keep the total volume constant. After 48 h, all aliquots were analyzed with help of a UV spectrophotometer (Model Lambda 35 - Perkin Elmer, United States) at the wavelength of 345 nm, as recommended elsewhere [20]. All tests were performed in triplicates.

Encapsulation Efficiency

To determine the encapsulation efficiency, 50 mg of the produced microparticles were added to 10 mL of distilled water and kept under slow magnetic stirring (with stirring speed ranging from 150-200 rpm) for 48 h at room temperature. After this period, the mixture was filtrated with a 0.45 [micro]m syringe filter and analyzed on a UV spectrophotometer (Model Lambda 35--Perkin Elmer, United States) at the wavelength of 345 nm. Concentrations were obtained by comparing UV readings with a standardized curve.

Flow Test

To illustrate the modification of the flow properties of gelatin solutions prepared in presence of doxycycline, aqueous gelatin solutions of different compositions were prepared under magnetic stirring and then sucked into a 1 mL pipette equipped with a pear. After removal of the pear, the time required for the material to flow through the pipette was measured with a stopwatch. All tests were performed at 30[degrees]C.

Particle Size Distribution

After dispersing 200 mg of the microparticles in 5 mL of ethanol, samples were analyzed through standard light scattering with help of a particle size analyzer (Malvern, Mastersizer 2000, United States) equipped with a helium neon laser source.


The morphology of the produced gelatin particles was analyzed by microphotography using the Stereoscopic Zoom Microscope (Nikon SMZ800, Japan).

GPC Analyzes

The chromatographic system comprised three OH-PAK SB806 (Shodex, Japan) columns connected in series, a Phenomenex TS-430 separation module (Phenomenex, United States) and a Viscotek VE358 refractive index detector (Malvern, United Kingdom). The running conditions and sample preparation procedures were defined in accordance with previously published material [26]. The mobile phase (18 g/L of SDS in Milli-Q water) was filtrated through 0.45 [micro]m filters prior to use.

Sample preparation consisted in dissolving I mg of gelatin in 1 mL of the SDS solution at room temperature. Before injection, all samples were filtrated through 0.22 [micro]m syringe filters. It is important to emphasize that clear and transparent solutions were obtained in all cases, so that gel formation could not be detected through visual inspection. Samples of 200 [micro]L were then injected into the GPC device and run for 80 min at flow rates of 0.5 mL/min at 40[degrees]C. The equipment was calibrated with poly(styrene sulfonate) standards provided by American Polymer Standards Corporation (United States) ranging from 31 to 2,260 kDa.


In this study, two types of commercial gelatins were used. The PhEur gelatin follows the specifications required by the European Pharmacopoeia and is a pharmaceutical grade gelatin. The Pigskin gelatin was selected to meet the gelatin specification normally required for encapsulation, with gel strength above 200 Bloom [6]. As gelatins may have distinct characteristics, depending on the source of collagen and production process, it is important to characterize these materials before use.

Table 1 shows the detailed amino acid composition of the analyzed gelatins, as provided by Biosynthesis (Texas, United States). As one can see in Table 1, the analyzed gelatins were not very different in terms of amino acid compositions, although small composition changes can affect significantly the concentration of a particular functional group.

Gelatins were also characterized by gel permeation chromatography (GPC), as shown in Fig. 1. As a whole, the obtained molar mass distributions were not very different; however, obtained results indicated that the molar mass distributions of the analyzed gelatins were formed by least four different populations, with different relative amounts in the two analyzed materials. This explains why the weight average molar mass (Mw) and polydispersity index (PI) of the PhEur gelatin were respectively equal to 196,607 g/gmol and 2.92, while the Mw and PI of the Pigskin gelatin were respectively equal to 155,895 g/gmol and 3.04. Therefore, the molar mass distribution of the Pigskin gelatin was shifted towards lower molecular weights, when compared to the molar mass distribution of the PhEur gelatin.

It is also important to know if gelatin is produced through acidic conditioning of collagen (type A gelatin) or through alkali conditioning of collagen (type B gelatin) [6]. Therefore, the pHs of aqueous solutions of the analyzed gelatins (0.1 g/mL) were measured to avoid reaction processing in the vicinities of the isoelectric points (IP). This precaution is necessary to allow for complete solubilization of gelatin in the aqueous phase. The results are shown in Table 2 and confirm that the analyzed gelatins belong to group A (acid gelatins) and are expected to dissolve in acidic media.

Type A gelatins have isoelectric points ranging between 7 and 9 [27]. This means that the aqueous phase pH during the reaction should not be above 7.0 to ensure the complete solubilization of the gelatins. As aqueous solutions (1 wt%) of doxycycline hyclate presents pH of 2.50, it can be assured that gelatin solubilization was not compromised in the present study.

After gelatin characterization, reactions were performed as indicated in Table 3. Runs were performed with distinct concentrations of crosslinking agents, distinct gelatins and different gelatin and drug concentrations.

In all experiments, sharp color modification of the doxycycline containing mixture was observed after adding gelatin into the aqueous phase, as shown in Fig. 2. As doxycycline chromophore groups are the enol and phenol groups [28], the functional groups of gelatin probably interact with these chromophore groups of doxycycline causing the color change. The pH values were also monitored during the transition phase, to ensure the acidic character of the reaction medium. In all case, pH values remained below 3.5, in the acidic region. Simultaneously, it was noted that the system viscosity seemed to increase after the color transition. To prove this observation, flow tests were performed as reported in Table 4. Obtained results for experiments 3A (before the color change) and 3B (after the color change) indicated that the flow time increased 45% after the color transition, confirming the increase of the system viscosity and the likely interaction between gelatin and doxycycline molecules.

It is common to associate the viscosity increase with the increase of average molar masses. For this reason, GPC analyzes of the initial and final products of Run#3, performed in absence of crosslinking agents, were performed, as shown in Fig. 3. According to previously reported results [29], average molar masses of gelatins treated thermally in presence of glucose and glycerol tend to decrease during treatment because of the residual modification of the characteristic triple helix structure of collagen. Similar results are presented in Fig. 3. This indicates that competitive mechanisms probably take place during the color transition phase and that interactions of gelatin with doxycycline are of physical nature, as the viscosity increase cannot be explained unequivocally in terms of the increase of average molar masses.

To determine if the proposed inverse suspension technique was able to stabilize and produce gelatin microparticles, particle size distribution analyzes were performed and microphotos were taken. Obtained results are shown in Table 5 and in Figs. 4-10.

Figure 4 shows morphological aspects of the analyzed gelatins, before the reactions. The microphotos indicate that the particles presented irregular shapes, probably because of the industrial gelatin extrusion process. Figure 4 also indicates that Pigskin gelatin particles were bigger than PhEur gelatin particles, as also confirmed in Fig. 5.

When Fig. 5 is compared with Figs. 6-10, which characterize the gelatin particles after treatment, it can be noticed in all cases that it was possible to modify the initial particle morphologies and to reduce the average particle sizes. This indicates that the proposed inverse suspension technique can be used to produce gelatin microparticles with more controlled size. As it might be expected, particles were larger when the gelatin concentration was higher and were not very sensitive to addition of crosslinking agents. Surprisingly, the average particle sizes of microparticles prepared with the Pigskin gelatin were much smaller than the average particle sizes of microparticles prepared with the PhEur gelatin, indicating the existence of differences between both gelatin samples that could not be captured with the analytical techniques used here.

Table 6 presents the encapsulation efficiency of doxycycline in the different runs. It can be noted that the lowest encapsulation efficiencies were obtained for reactions which used formaldehyde as a crosslinking agent (Run#l and Run#2). This can possibly be related to the longer reaction times and higher reaction temperatures, leading to more significant drug extraction by the oily phase, as doxycycline is soluble in water [28] and is also liposoluble [30]. In the other cases, encapsulation efficiency can be regarded as very high, given the relatively small amounts of gelatin and abundant use of acetone during dehydration.

Figure 11 shows drug release results obtained with microparticles obtained in Run#1 and Run#2. Figure 11 also shows results presented in an independent study for comparative purposes [20]. According to Fig. 11, the microparticles obtained in Run#l and Run#2 presented very similar dynamic release profiles (despite the different average diameters and different gelatins used) and much lower rates of drug release than reported by Melo and Pinto [20]. It is important to emphasize, though, that Melo and Pinto [20] did not report the gelatin properties and particle size diameters of obtained microparticles for proprietary reasons, although Runs #1 and #2 were performed at the same preparation conditions reported by Melo and Pinto for Test 39 [20]. It is also important to emphasize that the three experiments shown in Fig. 11 used different types of gelatin. Nonetheless, PhEur and Pigskin gelatins used in Run#1 and #2 were very similar in terms of amino acid composition and pH in solution, as already discussed, while these pieces of information were not provided by Melo & Pinto [20]. Therefore, although it is certain that one cannot provide unequivocal conclusions based on the available data, one can possibly conjecture that the observed differences indicate that the type of gelatin can affect both the encapsulation efficiencies and the rates of drug release (as particle sizes were very different for products of Run#1 and Run#2), due to the interactions that take place between the gelatin and doxycycline. It is also very important to observe that the rates of drug release were very slow (despite the small particle sizes) and followed typical first-order release trajectories, which apparently indicate that the rates of drug release were controlled by mass transfer constraints (probably related to mass transfer through the interfacial film, as doxycycline is very soluble in water and the particle size does not seem to affect the release profiles significantly). Particularly, the slow rates of drug release encourage the development of pharmaceutical tests in living models.

The increase of gelatin concentration (and increase of average particle sizes) did not affect the rates of drug release significantly, as also observed when release results obtained with the microparticles prepared in Run#5 and Run#3 were compared to each other, as shown in Fig. 12. This indicated once more that the release mechanism did not seem to be controlled solely by particle diffusion, as discussed previously. The increase of the particle diameter in Run#3 is probably related to the increase of the gelatin concentration and, consequently, of the viscosity of the initial gelatin solution. This prevents the formation of small particles, in spite of the higher amounts of surfactant in the recipe.

It is interesting to observe, as shown in Fig. 13, that addition of formaldehyde caused the drop of the encapsulation efficiency and did not lead to slower rates of doxycycline release, so that addition of formaldehyde did not exert any significant beneficial effect on the drug release system.

When all available controlled release data are analyzed simultaneously, as shown in Fig. 14, it can be noticed that the best results (the lowest rates of doxycycline release) were the ones obtained without addition of crosslinking agents. As a matter of fact, results published elsewhere [29] also indicated that addition of glucose exerted negligible effect on the course of gelatin thermal treatments, despite the frequent citation of glucose as an effective gelatin crosslinking agent. From a practical point of view, this can indeed constitute a very important processing advantage, as microparticle production can be performed in absence of external crosslinking agents, rendering the process cheaper and simpler. It is also very important to observe that less than 50% of the initial doxycycline charge had been released from the produced gelatin particles after 30 h of experimentation, which can be explored in future drug release applications.

Given'the slowest rates of drug release, the color modification of the doxycycline/gelatin solution and the increase of viscosity of the gelatin solution in presence of doxycycline, it can be assumed that strong physical interactions (because GPC analyzes did not confirm the increase of the average molar masses of gelatin treated with doxycycline) take place between the doxycycline chromophore groups and the functional groups of the gelatin. Since both enol and phenol chromophore groups present hydroxyl groups in their structures, as shown in Fig. 15, it seems reasonable to speculate that glycosidic bonds [31] can be formed between the OH groups of the gelatin and the OH groups of doxycycline. This might also explain why rates of drug release were higher in presence of glucose, as similar bonds might be formed with the OH groups of glucose, weakening the interaction between doxycycline and gelatin.


Doxycycline was encapsulated in situ with gelatin through thermal treatments performed in inverse suspension for the first time. Obtained results indicated that addition of formaldehyde and glucose to the reacting medium did not lead to increase of the characteristic doxycycline release time, as the best drug release profiles were obtained when no external crosslinking agent was added. This could be explained in terms of the physical interactions that take place between doxycycline and gelatin, as observed through distinct characterization procedures. From a practical point of view, this can constitute a very advantageous aspect of the proposed encapsulation process, as production of gelatin microparticles can be performed in absence of external crosslinking agents, rendering the process cheaper and simpler. It was also observed that less than 50% of the initial doxycycline charge was released from the produced gelatin particles after 30 h of experimentation, encouraging development of new drug release applications.


The authors thank CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil) and FAPERJ (Fundaqao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro, Brazil) for supporting this work and providing scholarships.


[1.] D.P. Andrade, D. Pallos, L.F.B.P. Forte, and L.H. Ricardo, Int. J. Dent., 8, 202 (2009).

[2.] N. Joshi, and D.Q. Miller, Arch. Intern. Med., 157, 1421 (1997).

[3.] D. Vargas-Estrada, J. Gracia-Mora, and H. Sumano, Res. Vet. Sci., 84, 477 (2008).

[4.] L. Gutierrez, D. Vargas-Estrada, C. Rosario, and H. Sumano, Br. Poult. Sci., 53, 366 (2002).

[5.] M. Lanza-Perea, M.K. Sachin, A. Sabarinath, S.E. Karpathy, R.N. Sharma, and D.M. Stone, West Indian Vet. J., 9, 11 (2009).

[6.] R. Schrieber and H. Gareis, Gelatine Handbook: Theory and Industrial Practice, Wiley-VCH, Weinheim, Germany (2007).

[7.] H. Fan and A.K. Dash, Int. J. Pharm., 213, 103 (2001).

[8.] S. Farris, J. Song, and Q. Huang, J. Agric. Food Chem., 58, 998 (2010).

[9.] K. Ulubayram, I. Eroglu, and N. Hasirci, J. Biomater. Appl., 16, 227 (2002).

[10.] A.L.T.C. Zampieri, E. Lima, and D.G.A. Diniz, Rev. Bras. Farmacia., 2, 73 (2005).

[11.] P. Davis and B. Tabor, J. Polym. Sci. Part A Gen., 1, 799 (1963).

[12.] R.A. Carvalho and C.R.F. Grosso, Brazilian J. Chem. Eng., 23, 45 (2006).

[13.] J.Y. Lai, J. Mater. Sci. Mater. Med., 21, 1899 (2010).

[14.] J.Y. Lai, J. Mech. Med. Biol., 11, 967 (2011).

[15.] E. Schacht, B. Bogdanov, A.V.D. Bulcke, and N. De Rooze, React. Fund. Polym., 33, 109 (1997).

[16.] R. Cortesi, E. Esposito, M. Osti, G. Squarzoni, E. Menegatti, and S.S. Davis, Eur. J. Pharm. Biopharm., 47, 153 (1999).

[17.] H. Wu, Z. Zhang, D. Wu, H. Zhao, K. Yu, and Z. Hou, J. Biomed. Mater. Res. Part B Appl. Biomater., 78, 56 (2006).

[18.] R. Cortesi, C. Nastruzzi, and S.S. Davis, Biomaterials, 19, 1641 (1998).

[19.] G.A. Digenis, T.B. Gold, and V.P. Shah, J. Pharm. Sci., 83, 915 (1994).

[20.] C.K. Melo, J.C.C. Pinto, Testes de Liberaqao com Nanoparticulas Polimercias Carregadas com Doxiciclina, Internal Report number 4, PEQ 13400, Fundaqao COPPETEC (in Portuguese).

[21.] F.A. Chaibva and R.B. Walker, Dissolution Technol., 14, 15 (2007).

[22.] M. Siewert, J. Dressman, C.K. Brown, V.P. Shah, J.M. Aiache, and N. Aoyagi, AAPS PharmSciTech, 4, 1 (2003).

[23.] C.T. Ueda, V.P. Shah, K. Derdzinski, G. Ewing, G. Flynn, and H. Maibach, PharmacopeiaI Forum, 35, 750 (2009).

[24.] Topical and Transdermal Drug Products - Product Performance tests. Pharmacopeial Forum, 35, 1 (2009).

[25.] R. Hanson, Dissolution Technol., 17, 33 (2010).

[26.] A.L. Dupont, J. Chromatogr. A, 950, 113 (2002).

[27.] GMIA, Gelatin Handbook, New York, Gelatin Manufacturers Institute of America (2002).

[28.] J.B. Bogardus, and R.K. Blackwood, J. Pharm. Sci., 68, 188 (1979).

[29.] D.V.Way, M.Nele, J.C.Pinto, Monitoring of Molar Mass Distributions of Gelatins Treated with Glucose and Glycerol (Submitted).

[30.] J. Fabre, P. Blanchard, and M. Rudhardt, Chemotherapy, 23, 129 (1977).

[31.] A.V.Demchenko, Handbook of Chemical Glycosylation: Advances in Stereoselectivity and Therapeutic Relevance, Wiley-VCH, Weinheim, Germany (2008).

Debora Vieira Way (iD),(1) Marcio Nele, (2) Jose Carlos Pinto (1)

(1) Programa de Engenharia Quimica/COPPE--Universidade Federal do Rio de Janeiro, Cidade Universitaria, CP:68502, Rio de Janeiro RJ 21941-972, Brazil

(2) Departamento de Engenharia Quimica/Escola de Quimica--Universidade Federal do Rio de Janeiro, Cidade Universitaria, CP:68502, Rio de Janeiro RJ 21941-909, Brazil

Correspondence to: J.C. Pinto; e-mail:

DOI 10.1002/pen.24628

Caption: FIG. 1. Mass molar distributions of the analyzed gelatins.

Caption: FIG. 2. Visual aspect of aqueous doxycycline solutions before (a), immediately after addition of gelatin (b) and after 5 min addition of gelatin (c). All pH measurementss were conducted at 60[degrees]C. [Color figure can be viewed at]

Caption: FIG. 3. Evolution of weight average molar mass in Run#3.

Caption: FIG. 4. Optical microphotos of (a) PhEur gelatin particles and (b) Pigskin gelatin particles.

Caption: FIG. 5. Particle size distribulions of the analyzed gelatins.

Caption: FIG. 6. Particle size distribution and optical microphoto of the final product of Run#1.

Caption: FIG. 7. Particle size distribution and optical microphoto of the final product of Run#2.

Caption: FIG. 8. Particle size distribution and optical microphoto of the final product of Run#3.

Caption: FIG. 9. Particle size distribution and optical microphoto of the final product of Run#4.

Caption: FIG. 10. Particle size distribution and optical microphoto of the final product of Run#5.

Caption: FIG. 11. Controlled release tests for products obtained in Test 39 [20], Run#1 and Run#2. [Color figure can be viewed at]

Caption: FIG. 12. Controlled release tests for products obtained in Run#3 and Run#5. [Color figure can be viewed at]

Caption: FIG. 13. Controlled release tests for products obtained in Run#l and Run#4. [Color figure can be viewed at]

Caption: FIG. 14. Controlled release tests for products obtained in Runs#1 to #5. [Color figure can be viewed at]

Caption: FIG. 15. Chemical structure of doxycycline.
TABLE 1. Amino acid composition of the analyzed gelatins.
                                 PhEur gelatin   Pigskin gelatin

                                  Composition      Composition
Aminoacid                           (mol%)           (mol%)

Hydroxyproline                      13.47            12.84
Aspartic acid and asparagine         5.51             5.25
Serine                               2.82             2.78
Glutamic acid and glutamine         10.11             9.72
Glycine                             21.18            21.51
Histidine                            1.32             1.33
Arginine                             8.67             8.84
Threonine                            1.86             1.85
Alanine                              8.60             8.54
Proline                             13.14            13.96
Cysteine                             0.00             0.00
Tyrosine                             0.65             0.86
Valine                               2.09             1.68
Methionine                           0.71             0.91
Lysine                               3.93             3.97
Isoleucine                           1.23             1.13
Leucine                              2.82             2.75
Phenylalanine                        1.99             2.08
Tryptophan                           0.00             0.00

TABLE 2. pH of aqueous gelatin solutions (0.1 g/mL).

Gelatin       pH      Classification   IP range (a)

PhEur        5.76         Type A          7 to 9
Pigskin      5.51

(a) According to Gelatin Manufacturers Institute of America GMIA

TABLE 3. Operation conditions used in drug encapsulation

                         SPAN80  Doxycycline  Formaldehyde  Glucose
Reaction   Type    (g)    (g)        (g)          (mL)        (g)

1         PhEur    1.5     1        0.75           2          0.5
2         Pigskin  1.5     1        0.75           2          0.5
3         PhEur    3.0     2         1.5           --         --
4         PhEur    1.5     I        0.75           --         0.5
5         PhEur    1.5     1        0.75           --         --

TABLE 4. Flow test results.

Experiment     Components      Mass (g)   time (s)

1            Distilled water      10         25
             PhEur gelatin       1.5

2            Distilled water      10         4
             Doxycycline         0.75

3A           Distilled water      10         29
             Doxycycline         0.75
             PhEur gelatin       1.5

3B           Distilled water      10         42
             Doxycycline         0.75
             PhEur gelatin       1.5

TABLE 5. Weight average diameters of produced gelatin particles.

Reaction     Diameter ([micro]m)

1                    240
2                    122
3                    474
4                    195
5                    210

TABLE 6. Encapsulation efficiency of doxycycline.

Reaction      Encapsulation efficiency (%)

1                          67
2                          49
3                          83
4                          88
5                          83
COPYRIGHT 2018 Society of Plastics Engineers, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2018 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Way, Debora Vieira; Nele, Marcio; Pinto, Jose Carlos
Publication:Polymer Engineering and Science
Article Type:Report
Date:May 1, 2018
Previous Article:Cellulose Nanofibril-Reinforced Polypropylene Composites for Material Extrusion: Rheological Properties.
Next Article:Multifunctional Greener Additives for Lubricating Oil.

Terms of use | Privacy policy | Copyright © 2021 Farlex, Inc. | Feedback | For webmasters |