There is no substitue for clean line for practice.
Othere then the pen tool, if you don't want to feel worn out and rigided, you just going to have to practice it. Some tips are to see ahead where you drawing and not to look at your pencil. Its almost like driving a car. You don't look like the nearest window, or else your car wobbles. You look at the distance.
Use your whole arm. For details, use your pinky for pivoting.
Also it ok to do work in layers. Do the mess first, then ink it. Some animators do a blue pencils for shape, and then the red for details. Then they would ink it. Or they usually do that all in pencil and then ink it.
Programs, well, pretty much anything. I like photoshop. Other people like sai. Some people like gimp. You can do pretty much the same thing in all of them, the difference is just how long it takes and how complicated it is.
I use Paint Tool Sai for everything. I start off with a rough sketch of whatever it is I want to draw. I normally do this in red so it's easy to see. Then I make a layer above the sketch and switch to black. I then change the stability to S-7. This adds a bit of a lag to the pencil or brush. The lines are produced slower which makes it easier to guide the lines to where you want them to go. After that I pretty much trace over the sketch.
Pretty much this is how I do it. All you need is a hard round brush and turning off the transfer. Here is a halfway work of mine. [link]
Create a sketch Change sketch color and opacity Make a new layer *Draw a line* Keep undoing until that line is perfect! Make a new layer Draw a line Edit the lines Merging layers together.
You can really speed up this process by using the actions window in photoshop. I personally have F2 set to create a new layer and F3 to merge down. This way you can punch through a ton of layers and merge them quickly. Alternatively you put each line on it's own layer and then merge.
Hi, Lots and lots of practice use a digital tablet use a large canvas size 2000-4000 pixels maybe 300 dpi small brush size confident brush strokes study color theory use layers plenty of youtube tutorials photoshop, sai, gimp... lots more practice