Controlled release systems aim at achieving a predictable and reproducible drug release profile over a desired time period. These controlled release formulations offer many advantages over conventional dosage forms. These advantages include: reduced dosing intervals, constant drug levels in the blood, increased patient compliance and decreased adverse effects. Complex controlled release formulations such as those with sustained release properties, often require additional steps during the production phase. The cost and economic impact associated with these complex controlled release dosage formulations often outweigh the short term benefits. Thus the development of an economic method to produce controlled release particles is of great importance especially in third world countries. In controlled release formulations the drug is often equally dispersed throughout a polymer matrix. In the presence of a thermodynamically compatible solvent, swelling occurs and the polymer releases its content to the surrounding medium. The rate of drug release can be controlled by interfering with the amount of swelling and rate of diffusion by manipulating the viscosity of the polymer matrix. Chitosan is an ideal candidate for controlled drug delivery through matrix release systems. It is a biodegradable polymer with absorption-enhancing properties. Cross-linking chitosan with different cross-linking agents allow the preparation of beads. Beads are frequently used in controlled release dosage forms as they are very flexible in dosage form development and show various advantages over single unit dosage forms. Because beads disperse freely in the gastrointestinal tract they maximize drug absorption, reduce fluctuation in peak plasma, and minimize potential side effects without lowering drug bio-availability. Chitosan beads and excipient containing chitosan beads were prepared and investigated as possible controlled release formulations. Pyrazinamide was chosen as the model drug. Chitosan beads and excipient containing chitosan beads were prepared by ionotropic gelation in tripolyphosphate. In this study chitosan/pyrazinamide beads containing pharmaceutical excipients (Ascorbic acid, Explotab and Ac-Di-Sol) were produced. The excipients were added individually and in combinations to the chitosadpyrazinamide dispersion and the beads were characterized on the basis of their morphology, solubility, fiability, drug loading capacity and swelling behaviour, as well as drug release (dissolution properties). The drug loading of the pyrazinarnide loaded chitosan beads, was 52.26 % 0.57%. It was noted that the inclusion of excipients in the beads resulted in an increase in drug loading with the combination of Ascorbic acid and Ac-Di-Sol giving the highest drug loading of 67.09 ± 0.22%. It was expected that the addition of the pharmaceutical excipients would lead to a sustained release of pyrazinamide. Dissolutions studies, however, revealed a burst release in both phosphate buffer solution (PBS) pH 5.60 and 7.40 over the first 15 minutes and the curve reached a plateau after 30 minutes. Thus, apparently the inclusion of the pharmaceutical excipients did not contribute to a sustained release of pyrazinamide over the tested period of six hours. In future studies the dissolution time can possibly be extended to a period of 24 hours. It might be possible for the remaining drug (approximately 40%) in the beads to be released over the extended period. Other polymers can also be investigated to control the release of pyrazinamide. Further studies are, however, necessary to investigate this possibility in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.

Antibiotic use is a vital method for the treatment of most diseases involving bacterial infections. Unfortunately, in certain cases these agents are not effective in treatments against diseases for either some limitation in antibiotic usage because of the side effects or some distribution problems caused by physiological or pathological barriers in the body. Such problems are thought to be minimized by development of controlled release systems which involve implantation of antibiotic loaded polymeric systems directly to the site of infection. Present study involves Vancomycin, a very strong antibiotic with a wide spectrum of activity, and two biocompatible and biodegradable polymers, poly(3-hydroxybutyrate-co-3-valerate) PHBV and poly(L-lactide-co-glycolide) PLGA, in the construction of rod shaped controlled release systems designed for the aim of local treatment of osteomyelitis. Vancomycin carrying rods of either PHBV 8 or PLGA (50:50) polymers were prepared by the use of cold paste and hot extrusion methods in two different loading ratios (2:1 and 1:1 P:V). In situ release kinetics of each type of rod was determined by spectrophotometric measurement of vancomycin concentration. For determination of drug content of the controlled release rods initially and at the end of the release experiments, extraction and IR (infrared) studies were carried out. The efficacy of the system was measured in vitro on the bacterial strain, B. subtilis. Characterization of the rods was made by the use of stereomicroscopy and SEM (scanning electron microscopy). In situ release results of the controlled Vancomycin release formulations revealed that for both polymer types, hot extrusion process enabled the formation of a more compact system that provided slower release of the agent compared to the cold paste method. With the combined effect of variable loading proportion and polymer type the most prolonged release was obtained by PHBV rods having 2:1, P:V, ratio (prepared by hot extrusion method). In general, the release kinetics from the rods obeyed the Fickian diffusion kinetics except for PLGA rods prepared by cold paste method with 1:1 and 2:1 (P:V) loading ratios, which had a first order rate of drug release. According to in vitro bioactivity assays, all the groups effectively inhibited bacterial growth with the first day release samples. On the seventh day, however, only two cold paste samples, PHBV:Vancomycin 1:1 and PLGA:Vancomycin 1:1 had drug content barely sufficient for MEC while the others were in the ineffective range. The IR and grinding-extraction studies proved that Vancomycin was still present within the rods after a ten day release period. The PHBV rods with 2:1 (P:V) ratio prepared by hot extrusion method seem to be the most promising drug delivery system in terms of providing prolonged release as an implantable drug delivery system for the treatment of bacterial infections of the bone, namely osteomyelitis.

Barley protein based microcapsules (1-5µm) incorporating fish oil/β-carotene were successfully prepared. Well suspended solid microcapsules, rather than emulsions, were able to form after high pressure emulsifying process. These wet-status microcapsules could be turned into dry powder by a spray drying process. The microcapsules demonstrated spherical shape and high loading capacity. Oxidative stability tests under accelerated conditions and in food formulations suggest barley proteins are effective microencapsulation materials to protect fish oil against oxidation. Microcapsule degradation and bioactive compound release behaviors were studied in the simulated gastro-intestinal tract. The data revealed that nano-encapsulations (20-30nm) were formed as a result of enzymatic degradation of microcapsule bulk matrix in the simulated gastric tract. These nano-encapsulations delivered β-carotene to a simulated human intestinal tract intact, where they were degraded by pancreatic enzymes and steadily released the β-carotene. These uniquely structured microcapsules may provide a new strategy to develop target delivery systems for nutraceuticals / Food Science and Technology

Introduction: Embolic agents are used to block blood flow of hypervascular tumours, ultimately resulting in target tissue necrosis. However, this therapy is limited by the formation of new blood vessels within the tumour, a process known as angiogenesis. Targeting angiogenesis led to the discovery of anti-angiogenic factors, large molecular weight proteins that can block the angiogenic process. The aim of this research is development of poly (vinyl alcohol) (PVA) aqueous solutions that cross-link in situ to form a hydrogel that functions as an embolic agent for delivery of macromolecular drugs. Methods: PVA (14 kDa, 83% hydrolysed), functionalised by 7 acrylamide groups per chain, was used to prepare 10, 15, and 20wt% non-degradable hydrogels, cured by UV or redox initiation. Structural properties were characterised and the release of FITCDextran (20kDa) was quantified. Degradable networks were then prepared by attaching to PVA (83% and 98 % hydrolysed) ester linkages with an acrylate end group. The effect on degradation profiles was assessed by varying parameters such as macromer concentration, cross-linking density, polymer backbone and curing method. To further enhance the technology, radiopaque degradable PVA was synthesised, and degradation profiles were determined. Cell growth inhibition of modified PVA and degradable products were also investigated. Results: Redox initiation resulted in non-degradable PVA networks of well-controlled structural properties. Increasing the solid content from 10 to 20wt% prolonged the release time from few hours to ~ 2 days but had no effect on the percent release, with only a maximum release of 65% achieved. Ester attachment to the PVA allowed flexibility in designing networks of variable swelling behaviors and degradation times allowing ease of tailoring for specific clinical requirements. Synthesis of radiopaque degradable PVA hydrogels was successful without affecting the polymer solubility in water or its ability to polymerize by redox. This suggested that this novel hydrogel is a potential liquid embolic with enhanced X-ray visibility. Degradable products had negligible cytotoxicity. Conclusion: Novel non-degradable and radiopaque degradable PVA hydrogels cured by redox initiation were developed in this research. The developed PVA hydrogels showed characteristics in vitro that are desirable for the in vivo application as release systems for anti-angiogenic factors.

Introduction: Embolic agents are used to block blood flow of hypervascular tumours, ultimately resulting in target tissue necrosis. However, this therapy is limited by the formation of new blood vessels within the tumour, a process known as angiogenesis. Targeting angiogenesis led to the discovery of anti-angiogenic factors, large molecular weight proteins that can block the angiogenic process. The aim of this research is development of poly (vinyl alcohol) (PVA) aqueous solutions that cross-link in situ to form a hydrogel that functions as an embolic agent for delivery of macromolecular drugs. Methods: PVA (14 kDa, 83% hydrolysed), functionalised by 7 acrylamide groups per chain, was used to prepare 10, 15, and 20wt% non-degradable hydrogels, cured by UV or redox initiation. Structural properties were characterised and the release of FITCDextran (20kDa) was quantified. Degradable networks were then prepared by attaching to PVA (83% and 98 % hydrolysed) ester linkages with an acrylate end group. The effect on degradation profiles was assessed by varying parameters such as macromer concentration, cross-linking density, polymer backbone and curing method. To further enhance the technology, radiopaque degradable PVA was synthesised, and degradation profiles were determined. Cell growth inhibition of modified PVA and degradable products were also investigated. Results: Redox initiation resulted in non-degradable PVA networks of well-controlled structural properties. Increasing the solid content from 10 to 20wt% prolonged the release time from few hours to ~ 2 days but had no effect on the percent release, with only a maximum release of 65% achieved. Ester attachment to the PVA allowed flexibility in designing networks of variable swelling behaviors and degradation times allowing ease of tailoring for specific clinical requirements. Synthesis of radiopaque degradable PVA hydrogels was successful without affecting the polymer solubility in water or its ability to polymerize by redox. This suggested that this novel hydrogel is a potential liquid embolic with enhanced X-ray visibility. Degradable products had negligible cytotoxicity. Conclusion: Novel non-degradable and radiopaque degradable PVA hydrogels cured by redox initiation were developed in this research. The developed PVA hydrogels showed characteristics in vitro that are desirable for the in vivo application as release systems for anti-angiogenic factors.

Thesis (M.Sc.(Tech.))--University of Waikato, 2006. / Includes bibliographical references (leaves 221-230) Also available via the World Wide Web.

The oral route of drug administration is most extensively used due to the obvious ease of administration. Verapamil hydrochloride is a WHO listed phenylalkylarnine, L-type calcium channel antagonist that is mainly indicated for cardiovascular disorders such as angina pectoris, supraventricular tachycardia and hypertension. Due to its relatively short half-life of approximately 4.0 hours, the formulation of a sustained-release dosage form is useful to improve patient compliance and to achieve predictable and optimized therapeutic plasma concentrations. Direct compression and wet granulation were initially used as methods for tablet manufacture. The direct compression method of manufacture produced tablets that exhibited formulation and manufacturing difficulties. Mini-tablets containing veraparnil hydrochloride were then prepared by wet granulation using Surelease® E-7-19010.and Eudragit® NE 30D as the granulating agents after which the granules were incorporated with an hydrophilic matrix material, Carbopol® 974P NF. Granule and powder blends were evaluated using the angle of repose, loose and tapped bulk density, Can's compressibility index, Hausner's ratio and drug content. Granules with good flow properties and satisfactory compressibility were used for further studies. Tablets were subjected to thickness, diameter and weight variation tests, crushing strength, tensile strength, friability and content uniformity studies. Tablets that showed acceptable pharmaco-technical properties were selected for further analysis. Drug content uniformity and dissolution release rates were determined using a validated isocratic HPLC method. Initially, USP apparatus 1 and 3 dissolution apparatus were used to determine in-vitro drug release rates from the formulations over a 22-hour period. USP apparatus 3 was finally selected as it offers the advantages of mimicking, in part, the changes in the physicochemical environment experienced by products in the gastro-intestinal tract. Differences in release rates between the test formulations and a commercially available product, Isoptin® SR were observed at different pH's using USP apparatus 1. The release of veraparnil hydrochloride from matrix tablets was pH dependent and was markedly reduced at higher pH values. This may be due, in part, to the poor solubility of veraparnil hydrochloride at these pH values and also the possible interaction of verapamil hydrochloride with anionic polymers used in these formulations. Swelling and erosion behaviour of the tablets were evaluated and differences in behaviour were observed which may be attributed to the physico-chemical characteristics of the polymers used in this study. In-vitro dissolution profiles were characterized by the difference (j1) and similarity factor (j2) and also by a new similarity factor, Sct. In addition, the mechanism of drug release from these dosage forms was mainly evaluated using the Korsmeyer-Peppas model and the kinetics of drug release assessed using other models, including Zero order, First order, Higuchi, HixsonCrowell, Weibull and the Baker-Lonsdale model. Dissolution kinetics were best described by application of the Weibull model, and the Korsmeyer-Peppas model. The release exponent, n, confirmed that drug release from these dosage forms was due to the mixed effects of diffusion and swelling and therefore, anomalous release kinetics are predominant. In conclusion, two test batches were found to be comparable to the reference product Isoptin® SR with respect to their in-vitro release profiles.

The use of minocycline for the treatment of a broad range of systemic infections and for severe acne has been associated with vestibular side effects. The severity of side effects may lead to poor adherence to therapy by patients. The use of sustained release formulations of minocycline that display slow dissolution of minocycline following administration may be beneficial in reducing the incidence and severity of side effects. Therefore, sustained release capsule dosage forms containing 100 mg minocycline (base) were manufactured and assessed for use as sustained release oral dosage forms of minocycline. Minocycline sustained release capsules were manufactured based on matrix technologies using hydroxypropylmethyl cellulose (HPMC) and Compritol® as release retarding polymers. The rate and extent of minocycline release from the capsules was evaluated using USP Apparatus 1 and samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection. Differences in the rate and extent of minocycline release from formulations manufactured using HPMC or Compritol® were influenced by the concentration of polymer used in the formulations. The rate and extent of minocycline release was faster and greater when low concentrations of polymer were used in formulations. The effect of different excipients on the release pattern(s) of minocycline and particularly their potential to optimise minocycline release from experimental formulations was investigated. The use of diluents such as lactose and microcrystalline cellulose (MCC) revealed that lactose facilitated minocycline release when HPMC was used as the polymer matrix. In contrast, the use of lactose as diluent resulted in slower release of minocycline from Compritol® based formulations. The addition of sodium starch glycolate to HPMC based formulations resulted in slower release of minocycline than when no sodium starch glycolate was used. Compritol® based formulations were observed to release minocycline faster following addition of sodium starch glycolate and Poloxamer 188 to experimental formulations. In vitro dissolution profiles were compared to a target or reference profile using the difference and similarity factors, ƒ1 and ƒ2 , and a one way analysis of variance (ANOVA). In addition, the mechanism of minocycline release was elucidated following fitting of dissolution data to the Korsmeyer-Peppas, Higuchi and Zero order models. Minocycline release kinetics were best described by the Korsmeyer-Peppas model and the values of the release exponent, n (italics), revealed that drug release was a result of the combined effects of minocycline diffusion through matrices and erosion of the matrices. These in vitro dissolution profiles were better fit to the Higuchi model than to the Zero order model. Two formulations that displayed a fit to the Zero order model were identified for further studies as potential dosage forms for sustained release minocycline.

A amilose, na presença de agentes complexantes adequados, tende a formar complexos de inclusão. Os mesmos são carregadores promissores, já que os ligantes aprisionados podem ser libertados posteriormente, o que conduz a muitas aplicações. Porém, a utilização da amilose nativa (AM) na formação dos complexos é limitada devido a sua baixa solubilidade em água. Sendo assim, estudos envolvendo a modificação desta molécula tornam-se promissores. O objetivo da presente tese foi preparar complexos de inclusão a partir da amilose nativa (AM) e modificada (AMA) usando como ligantes Rifampicina (RIF), Rodamina B (RB) e o Azul de Bromotimol (AB). Primeiramente, dentre os métodos existentes para modificação, escolheu-se a acetilação. O grau de acetilação foi investigado e a estrutura da amilose foi caracterizada por meio de FTIR, MEV, TGA e DSC. Quando comparada à AM, AMA apresentou maior solubilidade em água. A presença das bandas de absorção no FTIR à 1727, 1240 e 1122 cm-1, confirmaram a acetilação. Os resultados de MEV sugeriram que a superfície lisa da AM foi transformada em uma superfície mais áspera em AMA e as análises de TGA e DSC mostraram uma estrutura instável para a mesma. Após esta etapa os complexos foram produzidos e a influência da temperatura e dos ligantes foi avaliada através da caracterização físico-química. UV-vis, DLS, PZ e MEV foram as técnicas usadas neste processo. As análises de UV confirmaram a formação dos complexos e aqueles desenvolvidos na temperatura de 65°C foram mais eficientes. Dentre estes destacam-se aqueles complexos preparados com RIF. O diâmetro hidrodinâmico médio (dh) dos complexos medidos por DLS variou entre 70 e 100 nm, indicando que os mesmos podem ser utilizados em sistema de liberação controlada. Comparando o dh da AM e AMA, observou-se que os tamanhos são maiores após a complexação, o que pode indicar que para AMA ou a interação forma complexos mais compactos, ou os ligantes não interagiram com a AMA. Análise de PZ mostrou que os complexos AM-RB e AM-AB apresentam alta estabilidade (PZ < -30 mV) e que os demais complexos apresentam valores de PZ próximos da neutralidade, o que pode melhorar a adsorção dos mesmos em sistemas biológicos. Os complexos AMA-RB e AMA-AB não formaram complexos no estado sólido e os demais formaram uma estrutura amorfa após precipitação. Em conclusão, este estudo levou ao desenvolvimento de um método eficaz para a preparação de complexos de inclusão de amilose. / In the presence of suitable complexing agents, amylose tends to form inclusion complexes. This polymer is considered a promisor carrier since the ligands confined in its chains can be released later, leading to various applications. However, the use of native amylose (AM) in complexes formation is restricted due to its low water solubility. Therefore, studies regarding amylose modification become promising. The aim of this thesis was preparing inclusion complexes made of native (AM) and modified (AMA) amylose using rifampicin (RIF), rhodamine B (RB), and bromothymol blue (AB) as ligands. At first, acetylation was the chosen modification among the modified methods described in the literature. The acetylation degree was investigated and the modified macromolecule was characterized using FTIR, SEM, TGA, and DSC analysis. Compared with AM, AMA presented increased water solubility. The presence of absorption bands at 1727, 1240, and 1121 cm-1 confirmed the acetylation. SEM images suggested that the smooth surface of AM was turned into a rougher surface in AMA, while TGA and DSC results showed a less stable structure for AMA. After this step, the complexes were prepared and the influence of the temperature and ligand type was evaluated through physicochemical characterization. UV-Vis, DLS, PZ, and SEM were the techniques used in this process. UV-Vis analysis confirmed complexes formation, revealing that the ones prepared at 65°C were more efficient. Among those, complexes prepared with RIF stand out. The average hydrodynamic diameter (dh) of the complexes measured by DLS ranged from 70 to 100 nm, indicating that these complexes can be used in controlled release systems. Comparing the dh of AM and AMA, it was observed that the sizes were larger after complexation, which may indicate more compact complexes or no interaction between AMA and ligands. ZP results showed that AM-RB and AM-AB complexes presented high stability (PZ < -30 mV), while the others presented PZ values near neutrality, which can increase their adsorption in biological systems. AMA-RB and AMA-AB did not form complexes in solid state, while the others formed an amorphous structure after precipitation. In conclusion, this study leaded to an effective method development for the amylose inclusion complexes preparation.

Submitted by NATAN ROBERTO DE BARROS null (natan501@hotmail.com) on 2016-03-17T22:54:17Z No. of bitstreams: 1 DISSERTACAO FINAL - NATAN BARROS.pdf: 2287500 bytes, checksum: 5687ecdf1e7aabf2b962b2fed752c410 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-03-21T18:43:28Z (GMT) No. of bitstreams: 1 barros_nr_me_araiq.pdf: 2287500 bytes, checksum: 5687ecdf1e7aabf2b962b2fed752c410 (MD5) / Made available in DSpace on 2016-03-21T18:43:28Z (GMT). No. of bitstreams: 1 barros_nr_me_araiq.pdf: 2287500 bytes, checksum: 5687ecdf1e7aabf2b962b2fed752c410 (MD5) Previous issue date: 2016-02-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O látex extraído da seringueira Hevea brasiliensis têm mostrado promissores resultados em aplicações biomédicas, onde membranas produzidas deste material têm sido utilizadas como próteses e enxertos médicos devido às suas características de biocompatibilidade e estímulo natural à angiogênese. O objetivo desse trabalho consiste na incorporação de peptídeos em membranas de látex natural e no estudo de suas liberações. Esperamos com os resultados, viabilizar o uso do látex natural como sistema de liberação sustentada de peptídeos e/ou proteínas. A taxa de liberação dos peptídeos foi monitorada e quantificada por Cromatografia Líquida de Alta Eficiência (CLAE) em modo analítico. A incorporação do peptídeo às membranas de látex acompanhou diferentes caracterizações, dentre elas: Espectroscopia de Infravermelho por Transformada de Fourier (FTIR) que identificou a estabilidade dos peptídeos após incorporação ao látex natural pela preservação de bandas características para os peptídeos, dentre elas, as bandas 1643 – 1638 cm-1 deformação NH de aminas e C=O de amidas; 1524 - 1514 cm-1 deformação C=C de aromáticos; e 542 – 498 cm-1 deformação S-S, Capacidade de absorção de fluídos, Perda de massa em soluções aquosas, CLAE e Microscopia Eletrônica de Varredura (MEV). Durante os ensaios de liberação dos peptídeos pelas membranas de látex natural, observou-se a instabilidade dos peptídeos em solução, com degradação total em períodos que variaram de 48 a 120 horas nos valores de pH 7,4; 12,0; e água destilada (pH 5,6 – 6,4). Entretanto, para a solução de tampão acetato pH 4,0 não houve instabilidade dos peptídeos em solução. Desta forma, estes resultados sugerem a possível interferência causada por proteases alcalinas presentes no látex natural. Adicionalmente, com o propósito de eliminar das membranas o agente causador da degradação dos peptídeos, foram confeccionadas novas membranas submetidas ao tratamento de lavagem, e posteriormente os peptídeos foram adsorvidos às membranas. Durante os ensaios de liberação foi possível observar a liberação e a estabilidade dos peptídeos com liberação de 60% em 96 horas para o peptídeo desmopressina; 90% em 24 horas para somatostatina; 45% em 8 horas para ocitocina; e 80% em 24 horas para octreotida. A partir destes resultados podemos afirmar que o látex natural pode ser utilizado como matriz sólida na liberação tópica de peptídeos, no entanto, se faz necessária maior investigação sobre as enzimas proteolíticas presentes no látex natural extraído da seringueira Hevea brasiliensis. / The latex extracted from Hevea brasiliensis rubber tree have shown promising results in biomedical applications, where membranes produced from this material have been used as medical implants and grafts, due to its biocompatibility and natural stimulation of angiogenesis. The aim of this work was to incorporate peptides into natural latex membranes and the study of its release. We look forward to the results, enabling the use of natural latex as Controlled Release System of peptides and/or proteins. The rate of peptide release were monitored and quantified by High Performance Liquid Chromatography (HPLC) in an analytical way. The peptides incorporation into latex membranes followed different characterizations, such as: Fourier Transform Infrared Spectroscopy (FTIR) which identified the stability of peptides after incorporation into the natural latex by the preservation of characteristic bands for peptides, among them, 1643 - 1638 cm-1 NH strain of amines and amides C=O; 1524 - 1514 cm-1 strain C=C aromatic; and 542 - 498 cm-1 strain S-S, fluid absorption capacity, the loss in weight in aqueous solutions, HPLC and Scanning Electron Microscopy (SEM). During the release tests of peptides by the natural latex membranes, it was observed instability of the peptides in solution, with total extinction in periods that ranged between 48 and 120 hours in pH 7.4; 12.0; and distilled water (pH 5.6 - 6.4). However, for acetate buffer solution (pH 4.0) was not observed instability of peptides. Therefore, these results suggest that there are possible interferences caused by alkaline proteases present in the natural latex. Additionally, in order to remove the causative agent of degradation, were prepared new membranes subjected to washing treatment, and the peptides posteriorly adsorbed on the membranes. During the release tests, it was possible to observe the release and stability of peptides with 60% released at 96 hours for the peptide desmopressin; 90% in 24 hours for somatostatin; 45% in 8 hours for oxytocin; and 80% at 24 hours for octreotide. From these results we can say that the natural latex can be used as solid matrix in the topical & transdermal delivery of peptides, however, it is necessary further research into the proteolytic enzymes present in the natural latex extracted from the rubber tree Hevea brasiliensis.