02 处方设计.pptVIP

* * * With a wonderfully broad title such as this, you are probably thinking this guy can talk about pretty much anything he wants to!! The premise of my talk is that while approaching this topic with a formulation mindset (as this is my pharmacy background), I will address the task from standpoint of biopharmaceutics, physiology and lipid biochemistry as I believe these disciplines hold the key to optimising formulation design and clinical performance due to enhanced and reproducible oral bioavailability. * * Lastly, after access to the systemic circulation, there is the liklihood that some highly lipophilic drugs will associate with lipoproteins in the plasma and it is becoming apparent that this interaction can have a bearing on some pharmacokinetic and pharmacodynamic processes. It is not so much the formulation that will have an impact here, but rather the intrinsic properties of the formulated lipophilic drugs so that it is important to keep these factors in mind when interpretting the performance of the lipid-based dose form. Additiotnally, recognition of the likely interaction of lipophilic drugs with plasma lipoproteins will also hep with the devlopment of better pre-clinical progression strategies for such compounds. Having shown these three sequential factors, I will individually address some of the key aspects associated with each of them. * * 小结 对两因素问题A、B、C构成初始单纯形，在此三点上进行试验 规则1：去掉最坏点，用其对称反射点作新试点 例A、B、C中，A为最坏点，去掉A点并取A的对称点D点作为新试验点。 D＝[留下各点之和]－[去掉点]＝B＋C－A 在B、C、D三角形中继续使用规则1，如果C为坏点，去点C点，取其反点E，此时C、D、E三点又构成新的单纯形。 如果最坏点为D那么对称点就会返回到与A重合，此时改用规则2 * 规则2：去掉次坏点，用其对称反射点作新试点对称计算公式与前面相同 经过反复使用后，如果有一个点老是保留下来，必须使用规则3 规则3：重复、停止和缩短步长 一般一个点经3次单纯形后仍未被淘汰，它可能是一个很好点，也可能是偶然性或试验误差导致的假象。 此时需要重复试验：结果不好，淘汰；结果已很满意则停止试验 反之则以它为起点缩短步长，继续试验 * （2）多因素基本单纯形 设有n个因素n＋1个定点构成的n维空间单纯形，设有一点A=(a1, a2, a3, … an)，步长为a 则其余各点为： B=(a1+p,a2+q,a3+q,… … an+q) C=(a1+q,a2+p,a3+q,… … an+q) (n)=(a1+q,a2+q, … an-1+p, an+q) (n+1)=(a1+q,a2+q,a3+q,… … an+p) * 新点计算 同样