A Inseminação Artificial (IA) é a biotécnica que proporciona a maior pressão de seleção no melhoramento genético de um rebanho e, portanto deveria ser imprescindível na pecuária moderna. A ineficiência na detecção de estro e a baixa ciclicidade ovariana no período pós-parto constituem um grande entrave na aplicabilidade de programas de IA. Frente a estas dificuldades, o uso da Inseminação Artificial em Tempo Fixo (IATF) vem incrementando os resultados obtidos, uma vez que elimina a necessidade de observação de estro e induz a ciclicidade de vacas em anestro pós-parto. Nos protocolos de IATF é de fundamental importância o uso dos dispositivos intravaginais para liberação de progesterona (P4). No mercado atual, estes dispositivos importados são fabricados à base de silicone, um polímero biocompatível, porém não biodegradável. Recentemente, dispositivos intravaginais de P4, incorporada à matriz polimérica biodegradável de poli-hidroxibutirato (PHB), vêm sendo estudados. Este trabalho teve como objetivo comparar a eficiência, em programa de IATF, de um novo dispositivo intravaginal (Progestar®), na taxa de prenhez, em bovinos da raça Nelore, com a do dispositivo à base de silicone, DIB®, atualmente disponível no mercado brasileiro. Foram utilizadas 240 vacas da raça Nelore, em um delineamento de blocos casualizados generalizados, divididas em dois grupos (controle - DIB® e tratamento - Progestar®, usados nos protocolos de sincronização e IATF). Foram realizados 2 experimentos distintos: no primeiro experimento utilizaram-se dispositivos de 1º uso (n=136), enquanto que no segundo experimento, dispositivos de 2º uso (n=104). As taxas de prenhez, decorrentes da IATF (TPIATF) e ao final da estação de monta (TPEM) (variáveis dependentes), foram comparadas por análise de variância, separando o efeito de tratamento, dos blocos e das interações. No experimento 1: não houve interação das variáveis com o tratamento; não houve efeito de tratamento sobre a TPIATF (DIB® - 66,7% e Progestar® - 65,8%) nem sobre a TPEM (DIB® - 95% e Progestar® - 94,7%); houve interação entre período pós-parto (PPP) e escore de condição corporal (ECC). Animais no PPP1 (45 a 70 dias) e ECC4 apresentaram resultados inferiores na TPIATF em relação aos animais ECC5 e 6; houve também interação entre PPP e escore de condição ovariana (ECO), em que animais no PPP2 (71 a 90 dias) que não estavam ciclando apresentaram resultados inferiores de TPIATF, em relação aos animais ciclando; e também não houve efeito das demais variáveis sobre a TPIATF e TPEM. No experimento 2: não houve interação das variáveis com o tratamento; não houve efeito de tratamento sobre a TPIATF (DIB® 2 - 61,6% e Progestar® 2 - 55,8%) nem sobre a TPEM (DIB® 2 - 94,2% e Progestar® 2 - 88,5%); houve interação entre categoria animal (Cat) e PPP, em que primíparas no PPP1 (32 a 55 dias) apresentaram resultados inferiores na TPEM em relação às primíparas no PPP2 (56 a 90 dias); houve também interação entre PPP e ECC, em que animais no PPP2 e com ECC4 apresentaram resultados inferiores de TPEM, em relação aos animais com ECC5; e também houve efeito negativo do PPP1 sobre a TPIATF e de um dos touros na TPEM. Após a realização do experimento concluiu-se que o Progestar® possui semelhante eficiência na taxa de prenhez, quando comparado ao DIB® e que ambos tratamentos têm potencial para proporcionar TPIATF acima de 50% e TPEM acima de 90%. / The artificial insemination (AI) is a biotechnique that causes the fastest genetic improvement of a herd and, therefore should be essential in the modern livestock. Heat detection inefficiency and low ovarian ciclicity in the postpartum period establish a great obstacle on applicability of AI programs. In front of these difficulties, the use of timed artificial insemination (TAI) improves the results, because eliminates the heat detection and induces the ciclicity of cows in anestrous postpartum. In TAI protocols is fundamental the use of intravaginal devices for releasing progesterone (P4). In the current market, these devices are imported and made of silicone, a biocompatible polymer, but not biodegradable. Recently intravaginal progesterone devices made of PHB, a biodegradable polymer, have been studied. The aim of this study was to compare the efficiency, in TAI program, of a new intravaginal device (Progestar®), on pregnancy rate, in Nelore cows, with a device made of silicone DIB®, currently available in the brazilian market. Were used 240 Nelore cows, in a generalized randomized block design, divided in two groups (control - DIB® and treatment - Progestar®, used in the synchronization protocols and TAI). Two experiments were done: the first experiment used new intravaginal devices (n=136), while the second experiment utilized used intravaginal devices (n=104). The pregnancy rates, of TAI (TAIPR) and breeding season (BSPR) (dependent variables), were compared by analysis of variance, separating the treatment, blocks and interactions effect. In experiment 1: there was no interaction between variables and treatment; there was no effect of treatment on TAIPR (DIB® - 66,7% and Progestar® - 65,8%) and on BSPR (DIB® - 95% and Progestar® - 94,7%); there was an interaction between postpartum period (PPP) and body condition score (BCS), in which animals in PPP1 (45 to 70 days) and BCS4 showed inferior results on TAIPR related to animals BCS5 and 6; there was also an interaction between PPP and ovary condition score (OCS), in which animals in PPP2 (71 to 90 days) not cyclic showed inferior results on TAIPR, related to cyclic animals; and there was also no effect of variables on TAIPR and BSPR. In experiment 2: there was no interaction between variables and treatment; there was no effect of treatment on TAIPR (DIB® 2 - 61,6% and Progestar® 2 - 55,8%) and on BSPR (DIB® 2 - 94,2% and Progestar® 2 - 88,5%); there was an interaction between animal category (Cat) and PPP, in which primiparous in PPP1 (32 to 55 days) showed inferior results on BSPR, related to primiparous in PPP2 (56 to 90 days); there was also an interaction between PPP and BCS, in which animals in PPP2 and BCS4 showed inferior results on BSPR, related animals BCS5; and there was also negative effect of PPP1 on TAIPR and one of the bulls on BSPR. This experiment showed that the Progestar® had the same efficiency on pregnancy rate, as the commercially available DIB® and both treatments have the potential to provide TAIPR above 50% and BSPR above 90%.

A Inseminação Artificial (IA) é a biotécnica que proporciona a maior pressão de seleção no melhoramento genético de um rebanho e, portanto deveria ser imprescindível na pecuária moderna. A ineficiência na detecção de estro e a baixa ciclicidade ovariana no período pós-parto constituem um grande entrave na aplicabilidade de programas de IA. Frente a estas dificuldades, o uso da Inseminação Artificial em Tempo Fixo (IATF) vem incrementando os resultados obtidos, uma vez que elimina a necessidade de observação de estro e induz a ciclicidade de vacas em anestro pós-parto. Nos protocolos de IATF é de fundamental importância o uso dos dispositivos intravaginais para liberação de progesterona (P4). No mercado atual, estes dispositivos importados são fabricados à base de silicone, um polímero biocompatível, porém não biodegradável. Recentemente, dispositivos intravaginais de P4, incorporada à matriz polimérica biodegradável de poli-hidroxibutirato (PHB), vêm sendo estudados. Este trabalho teve como objetivo comparar a eficiência, em programa de IATF, de um novo dispositivo intravaginal (Progestar®), na taxa de prenhez, em bovinos da raça Nelore, com a do dispositivo à base de silicone, DIB®, atualmente disponível no mercado brasileiro. Foram utilizadas 240 vacas da raça Nelore, em um delineamento de blocos casualizados generalizados, divididas em dois grupos (controle - DIB® e tratamento - Progestar®, usados nos protocolos de sincronização e IATF). Foram realizados 2 experimentos distintos: no primeiro experimento utilizaram-se dispositivos de 1º uso (n=136), enquanto que no segundo experimento, dispositivos de 2º uso (n=104). As taxas de prenhez, decorrentes da IATF (TPIATF) e ao final da estação de monta (TPEM) (variáveis dependentes), foram comparadas por análise de variância, separando o efeito de tratamento, dos blocos e das interações. No experimento 1: não houve interação das variáveis com o tratamento; não houve efeito de tratamento sobre a TPIATF (DIB® - 66,7% e Progestar® - 65,8%) nem sobre a TPEM (DIB® - 95% e Progestar® - 94,7%); houve interação entre período pós-parto (PPP) e escore de condição corporal (ECC). Animais no PPP1 (45 a 70 dias) e ECC4 apresentaram resultados inferiores na TPIATF em relação aos animais ECC5 e 6; houve também interação entre PPP e escore de condição ovariana (ECO), em que animais no PPP2 (71 a 90 dias) que não estavam ciclando apresentaram resultados inferiores de TPIATF, em relação aos animais ciclando; e também não houve efeito das demais variáveis sobre a TPIATF e TPEM. No experimento 2: não houve interação das variáveis com o tratamento; não houve efeito de tratamento sobre a TPIATF (DIB® 2 - 61,6% e Progestar® 2 - 55,8%) nem sobre a TPEM (DIB® 2 - 94,2% e Progestar® 2 - 88,5%); houve interação entre categoria animal (Cat) e PPP, em que primíparas no PPP1 (32 a 55 dias) apresentaram resultados inferiores na TPEM em relação às primíparas no PPP2 (56 a 90 dias); houve também interação entre PPP e ECC, em que animais no PPP2 e com ECC4 apresentaram resultados inferiores de TPEM, em relação aos animais com ECC5; e também houve efeito negativo do PPP1 sobre a TPIATF e de um dos touros na TPEM. Após a realização do experimento concluiu-se que o Progestar® possui semelhante eficiência na taxa de prenhez, quando comparado ao DIB® e que ambos tratamentos têm potencial para proporcionar TPIATF acima de 50% e TPEM acima de 90%. / The artificial insemination (AI) is a biotechnique that causes the fastest genetic improvement of a herd and, therefore should be essential in the modern livestock. Heat detection inefficiency and low ovarian ciclicity in the postpartum period establish a great obstacle on applicability of AI programs. In front of these difficulties, the use of timed artificial insemination (TAI) improves the results, because eliminates the heat detection and induces the ciclicity of cows in anestrous postpartum. In TAI protocols is fundamental the use of intravaginal devices for releasing progesterone (P4). In the current market, these devices are imported and made of silicone, a biocompatible polymer, but not biodegradable. Recently intravaginal progesterone devices made of PHB, a biodegradable polymer, have been studied. The aim of this study was to compare the efficiency, in TAI program, of a new intravaginal device (Progestar®), on pregnancy rate, in Nelore cows, with a device made of silicone DIB®, currently available in the brazilian market. Were used 240 Nelore cows, in a generalized randomized block design, divided in two groups (control - DIB® and treatment - Progestar®, used in the synchronization protocols and TAI). Two experiments were done: the first experiment used new intravaginal devices (n=136), while the second experiment utilized used intravaginal devices (n=104). The pregnancy rates, of TAI (TAIPR) and breeding season (BSPR) (dependent variables), were compared by analysis of variance, separating the treatment, blocks and interactions effect. In experiment 1: there was no interaction between variables and treatment; there was no effect of treatment on TAIPR (DIB® - 66,7% and Progestar® - 65,8%) and on BSPR (DIB® - 95% and Progestar® - 94,7%); there was an interaction between postpartum period (PPP) and body condition score (BCS), in which animals in PPP1 (45 to 70 days) and BCS4 showed inferior results on TAIPR related to animals BCS5 and 6; there was also an interaction between PPP and ovary condition score (OCS), in which animals in PPP2 (71 to 90 days) not cyclic showed inferior results on TAIPR, related to cyclic animals; and there was also no effect of variables on TAIPR and BSPR. In experiment 2: there was no interaction between variables and treatment; there was no effect of treatment on TAIPR (DIB® 2 - 61,6% and Progestar® 2 - 55,8%) and on BSPR (DIB® 2 - 94,2% and Progestar® 2 - 88,5%); there was an interaction between animal category (Cat) and PPP, in which primiparous in PPP1 (32 to 55 days) showed inferior results on BSPR, related to primiparous in PPP2 (56 to 90 days); there was also an interaction between PPP and BCS, in which animals in PPP2 and BCS4 showed inferior results on BSPR, related animals BCS5; and there was also negative effect of PPP1 on TAIPR and one of the bulls on BSPR. This experiment showed that the Progestar® had the same efficiency on pregnancy rate, as the commercially available DIB® and both treatments have the potential to provide TAIPR above 50% and BSPR above 90%.

Drug delivery technology is currently advancing faster than at any time in biotechnology history. The challenge of drug delivery is to achieve a controlled release of therapeutic agents over an extended period. Controlled release potentially offers significant advantages over conventional dosage forms, by eliminating both under- and overdosing while maintaining a desired range of drug concentrations. An existing drug regimen for induced calving produces a declining blood profile that does not mimic the naturally occurring, gradually increasing, cortisol blood level around parturition effectively, causing animal health issues. Likewise, while the existing progesterone controlled release systems for oestrous control successfully synchronise oestrus, it is however, associated with reduced fertility and as such other drugs have to be administered to improve the fertility during oestrus. Therefore, there is a need for a drug delivery system that is capable of delivering multiple drugs at various times and patterns. This research aimed to investigate, characterize, identify steroids with high absorption rates through vaginal mucosa and evaluate the potential of an electronic drug delivery system for the delivery of steroids for either the control of the bovine oestrous cycle or induced calving. In order to identify steroids with high absorption rates across the vaginal mucosa, an in vitro permeation method was developed to screen selected steroids for their ability to permeate artificial and biological membranes. The steroids were pre-formulated to enhance their solubility and permeation through these membranes. Analytical UV and HPLC assays to characterise the pure and formulated steroidal compounds were also developed and validated. An assessment of an intravaginal Electronically Modulated Intravaginal Device (EMID) for the control of the bovine oestrous cycle or induced calving was carried out. Five different release assessment methods were investigated and critically evaluated in order to identify the most appropriate release assessment method for the EMID. These were: 1) the Drug Dissolution Test, 2) a weight loss method, 3) the dispensed weight method, 4) the determination of piston travel distance method, and 5) the rod expulsion from the EMID method. The methods investigated were critically evaluated in terms of ease of use and automation, reproducibility and cost/time savings. Optimisation of various components and construction materials of the EMID were also investigated. Animal trials were carried out using the original EMID (manufactured from polypropylene polymer) and modified inserts (manufactured from high density polyethylene polymer) to determine their retention rate in the animals. Accelerated stability testing of progesterone in suspension, oestradiol-17 tablets, cloprostenol as a powder blend and the driving mechanism of the EMID were examined. The flux of the steroids was evaluated through poly-&-caprolactone and excised cow mucosa membranes using side-by-side permeation cells. Results indicated that progesterone followed by dexamethasone acetate and dexamethasone valerate showed higher permeability values through vaginal mucosa compared to dexamethasone or its other analogues. The weight loss method of the EMID proved to be an easy and appropriate method to measure the release rate from the EMID. A high density polyethylene polymer was identified as the most ideal body material for the insert compared to polypropylene body. Also double O-ring silicone, Elastollan WYO 1388-5 and solid silicone pistons were found to be amongst the best pistons tested and all performed well compared to other piston materials. There was a low retention rate with either the original EMID or the modified inserts. Further modification of retention wings of the EMID did not improve the retention rate, but a good blood profile response was obtained from cows treated with the complete EMID containing formulated progesterone. The formulations and driving mechanism were found to be stable under the tested conditions. Therefore, the EMID has potential for commercial application of induced calving or oestrous control per vaginum administration, reliant on improvement of its retention mechanism.